1887

Chapter 49 : Integration, Regulation, and Long-Term Stability of R2 Retrotransposons

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in
Zoomout

Integration, Regulation, and Long-Term Stability of R2 Retrotransposons, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555819217/9781555819200_Chap49-1.gif /docserver/preview/fulltext/10.1128/9781555819217/9781555819200_Chap49-2.gif

Abstract:

R2 elements exclusively insert into 28S rRNA genes ( Figure 1 ). As a result of this specificity, R2 is one of the more tractable mobile elements to study and, thus, is now among the best understood elements both in terms of its mechanism and its population dynamics. The R2 element was first identified in the rDNA loci of in the early 1980’s ( ), when little was known of the structure or abundance of mobile elements in eukaryotes. In fact, the exclusive residence of the element at a specific site in the 28S gene initially suggested that it might be an intron. However, the findings that only a fraction of the genes contained the insertion, that 28S genes containing the insertion did not appear to be transcribed, and that many of the insertions had a sizeable deletion at the 5′ end all argued against its role as an intron. Insertions were soon identified at the same position of the 28S rRNA gene in many other species of insects ( ). The complete sequence of the insertions in both and revealed a large open reading frame (ORF) encoding a reverse transcriptase that had greatest sequence similarity to that of non-LTR retrotransposons ( ). R2 differed from most non-LTR retrotransposons, however, in that it only contained a single ORF. Furthermore, rather than an encoded apurinic endonuclease (APE) located amino-terminal to the reverse transcriptase ( ), R2 encoded carboxyl terminal to the reverse transcriptase an endonuclease with an active site more similar to that of certain restriction enzymes ( ).

Citation: Eickbush T, Eickbush D. 2015. Integration, Regulation, and Long-Term Stability of R2 Retrotransposons, p 1127-1146. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0011-2014
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of Figure 1
Figure 1

R2 elements insert within the 28S rRNA genes. The nucleolus, the site of rRNA transcription and processing, is organized around the hundreds of tandem units (rDNA units) that comprise the rDNA locus. Each rDNA unit is composed of a single transcription unit containing the 18S, 5.8S, and 28S genes (black boxes) and external and internal transcribed spacers (white boxes). The transcription units are separated by intergenic spacers (thin lines). A subset of the 28S genes in many animals contain R2 insertions near the middle of the gene (red box). R2 elements encode a single open reading frame (ORF).

Citation: Eickbush T, Eickbush D. 2015. Integration, Regulation, and Long-Term Stability of R2 Retrotransposons, p 1127-1146. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0011-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2
Figure 2

Domain structure of the R2 protein and its similarity to other elements. At the bottom is the R2 element from with the 5′ and 3′ untranslated regions indicated by dotted lines. The central region of the encoded protein contains the reverse transcriptase domain. The various conserved motifs within the fingers and palm regions (motifs 1–7) and the predicted thumb are indicated. An RNA binding domain is immediately N-terminal to the reverse transcriptase and conserved motifs within this domain are labeled 0 and −1. The N-terminal region of the protein contains zinc finger (Zn) and c-myb (Myb) motifs, while the C-terminal region encodes a putative zinc-binding domain and the R2 endonuclease. Shown below the R2 diagram are the 5′ and 3′ regions of the R2 RNA that are bound by the R2 protein during a retrotransposition reaction (see Figure 4 ). The major difference among R2 elements from different species is the presence of one, two, or three zinc finger domains at the N-terminal end. The R2 element from horseshoe crab is an example of the latter. Comparison of the R2 protein with the gene of LTR retrotransposons (and retroviruses) reveals little in common except for 7 out of the 9 motifs in the reverse transcriptase domain. Most LTR retrotransposon genes also encode an RNase H and integrase not found in R2. The R2 protein has greater similarity to the proteins encoded by group II introns and telomerases. These three groups share all nine motifs of the reverse transcriptase. In the case of telomerase, these motifs are frequently termed 1, 2, 3, A, IFD, B, C, D, and E (from left to right) ( ). Group II introns, telomerases, and R2 also share an RNA binding domain upstream of the reverse transcriptase (purple segment). Group II introns and R2 both encode an endonuclease domain at the 3′ end, while R2 and some telomerases have DNA binding domains (TEN) at the N-terminal end.

Citation: Eickbush T, Eickbush D. 2015. Integration, Regulation, and Long-Term Stability of R2 Retrotransposons, p 1127-1146. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0011-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3
Figure 3

The R2 ribozyme. (A) An rDNA transcription unit is diagramed with 18S, 5.8S, and 28.S genes (gray boxes), transcribed spacers (white boxes), and R2 insertion (black box). All three rRNAs are normally processed from the single primary transcript. When a unit contains an R2 insertion, a self-cleaving ribozyme encoded at the 5′ end of the element releases the 5′ end of the R2 transcript from the upstream 28S rRNA sequence. It is not known if transcription ends at the 3′ end of the R2 element, or if this end is processed from downstream 28S gene sequences. (B) On the left is the R2 ribozyme folded in a structure similar to that of the hepatitis delta virus (HDV) ribozyme ( ). The various components of the ribozyme are labeled as in the HDV ribozyme: P, base-paired region; L, loop; J, nucleotides joining paired regions. 28S gene sequences are shaded with gray. On the right is the R2 ribozyme from (earwig). Self-cleavage (arrow) occurs at the precise junction of the R2 element with the 28S gene in the case of the element and upstream of the junction in the 28S gene sequences in the case of the R2 element from .

Citation: Eickbush T, Eickbush D. 2015. Integration, Regulation, and Long-Term Stability of R2 Retrotransposons, p 1127-1146. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0011-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 4
Figure 4

The R2 retrotransposition model. An R2 integration reaction is proposed to involve symmetric cleavage/DNA synthesis steps by R2 proteins bound upstream and downstream of the insertion site. From top to bottom, protein bound upstream of the insertion site is associated with the 3′ end of the R2 transcript. This protein both cleaves the bottom stand of DNA and catalyzes the reverse transcription of the R2 RNA using the cleaved DNA target as primer, target primed reverse transcription (TPRT). R2 protein bound downstream of the insertion site is associated with the 5′ end of the R2 transcript. When the reverse transcription reaction catalyzed by the upstream protein dislodges the 5′ RNA, the downstream protein cleaves the top DNA strand and again uses the cleaved DNA to prime second strand DNA synthesis. Second strand synthesis requires the polymerase to displace the R2 RNA. Because in the absence of bound RNA the downstream protein does not bind tightly to the DNA target, it is shown dissociated from the target site during polymerization. The integration reaction is completed by the host repair machinery which fills in the single stranded gaps at the target site. Blue oval, protein subunit (dark, active; light, inactive); wavy black line, R2 RNA; dashed red lines, synthesized DNA; solid black lines; target DNA.

Citation: Eickbush T, Eickbush D. 2015. Integration, Regulation, and Long-Term Stability of R2 Retrotransposons, p 1127-1146. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0011-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 5
Figure 5

Variation in the priming of second-strand DNA synthesis. R2 elements differ in whether the 5′ end of the RNA template used in the integration reaction ends at the boundary between R2 and the 28S gene or extends a short distance upstream in the 28S rRNA sequence. This difference is dependent upon the location of the self-cleavage site by the R2 ribozyme (see text). Left panel. If self-cleavage by the R2 ribozyme is upstream in the 28S gene sequences, the resulting cDNA strand can form a heteroduplex with the upstream target DNA. This heteroduplex can stabilize the integration intermediate resulting in precise initiation of second strand synthesis (arrow) and uniform 5′ ends for different R2 copies. Right panel. If self-cleavage is at the 28S/R2 junction, there are no 28S sequences on the DNA strand (cDNA) generated by reverse transcription. As a consequence, the R2 protein must use regions of microhomology to initiate second strand synthesis (arrow). Priming frequently involves the 3–5 non-templated nucleotides added to the cDNA strand as the enzyme ran off the RNA template (lower case n’s). This use of chance microhomologies to prime second strand DNA synthesis gives rise to sequence variation at the 5′ junctions of different integrated copies of R2. Wavy black line, RNA with 5′ end denoted; red dashed line, first strand DNA composed of R2 sequences; gray box, first strand DNA sequences complementary to upstream DNA target sequences.

Citation: Eickbush T, Eickbush D. 2015. Integration, Regulation, and Long-Term Stability of R2 Retrotransposons, p 1127-1146. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0011-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 6
Figure 6

The transcription domain model of the rDNA locus and the long-term stability of R2 elements. (A) Uninserted (black boxes) and R2-inserted (black boxes with red insert) rDNA units are interspersed throughout the tandem array of rRNA genes. In Drosophila, a contiguous region of the rDNA locus with the lowest level of R2 insertions is selected for transcription. For simplicity this region is drawn as only seven units, but in it is believed to be about 40 units. The remainder of the locus is packaged into heterochromatin (the compacted DNA plus protein flanking the active region). If the region selected as the transcription domain is free of R2-inserted units, then there is no R2 transcription and no R2 retrotransposition. (B) The driving force in the concerted evolution of the rDNA locus is crossovers between chromosomes. Most of these crossovers occur within the transcription domain (see text). The diagramed crossover produces one chromosome with an expanded R2 free region. Because the same number of rDNA units is still activated for transcription, some of the units that were transcribed before the crossover are packaged into heterochromatin after the crossover. Asterisks marking the original boundary of the transcription domain show this shift. The other chromosome product of the recombination contains an rDNA locus with a smaller R2-free region. In this case, rDNA units originally flanking the transcription domain are now activated for transcription. These flanking units contain R2 inserted units and thus copies of the R2 element are transcribed and retrotranspositions result.

Citation: Eickbush T, Eickbush D. 2015. Integration, Regulation, and Long-Term Stability of R2 Retrotransposons, p 1127-1146. In Craig N, Chandler M, Gellert M, Lambowitz A, Rice P, Sandmeyer S (ed), Mobile DNA III. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MDNA3-0011-2014
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781555819217.chap49
1. Dawid IB,, Rebbert ML . 1981. Nucleotide sequence at the boundaries between gene and insertion regions in the rDNA of D. melanogaster . Nucleic Acids Res 9 : 5011 5020.[PubMed] [CrossRef]
2. Roiha H,, Miller JR,, Woods LC,, Glover DM . 1981. Arrangements and rearrangements of sequence flanking the two types of rDNA insertion in D. melanogaster . Nature 290 : 749 753.[PubMed] [CrossRef]
3. Smith VL,, Beckingham K . 1984. The intron boundaries and flanking rRNA coding sequences of Calliphora erythrocephala rDNA. Nucleic Acids Res 12 : 1707 1724.[PubMed] [CrossRef]
4. Fujiwara H,, Orgura T,, Takada N,, Miyajima N,, Ishikawa H,, Maekawa H . 1984. Introns and their flanking sequences of B. mori rDNA. Nucleic Acids Res 12 : 6861 6869.[PubMed] [CrossRef]
5. Eickbush TH,, Robins B . 1985. B. mori 28S genes contain insertion elements similar to the type I and type II elements of D. melanogaster . EMBO J 4 : 2281 2285.[PubMed]
6. Burke WD,, Calalang CC,, Eickbush TH . 1987. The site-specific ribosomal insertion element type II of Bombyx mori (R2Bm) contains the coding sequence for a reverse transcriptase-like enzyme. Mol Cell Biol 7 : 2221 2230.[PubMed]
7. Jakubczak JL,, Xiong Y,, Eickbush TH . 1990. Type I (R1) and Type II (R2) ribosomal DNA insertions of Drosophila melanogaster are retrotransposable elements closely related to those of Bombyx mori . J Mol Biol 212 : 37 52.[PubMed] [CrossRef]
8. Feng Q,, Moran JV,, Kazazian HH,, Boeke JD . 1996. Human L1 retrotransposon encodes a conserved endonuclease required for retrotransposition. Cell 87 : 905 916.[PubMed] [CrossRef]
9. Yang J,, Malik HS,, Eickbush TH . 1999. Identification of the endonuclease domain encoded by R2 and other site-specific, non-long terminal repeat retrotransposable elements. Proc Natl Acad Sci USA 96 : 7847 7852.[PubMed] [CrossRef]
10. Jakubczak JL,, Burke WD,, Eickbush TH . 1991. Retrotransposable elements R1 and R2 interrupt the rRNA genes of most insects. Proc Natl Acad Sci USA 88 : 3295 3299.[PubMed] [CrossRef]
11. Burke WD,, Malik HS,, Jones JP,, Eickbush TH . 1999. The domain structure and retrotransposition mechanism of R2 elements are conserved throughout arthropods. Mol Biol Evol 16 : 502 511.[PubMed] [CrossRef]
12. Kojima KK,, Fujiwara H . 2004. Cross-genome screening of novel sequence-specific non-LTR retrotransposons: various multicopy RNA genes and microsatellites are selected as targets. Mol Biol Evol 21 : 207 217.[PubMed] [CrossRef]
13. Kojima KK,, Kuma K,, Toh H,, Fujiwara H . 2006. Identification of rDNA-specific non-LTR retrotransposons in Cnidaria. Mol Biol Evol 23 : 1984 1993.[PubMed] [CrossRef]
14. Luchetti A,, Mantovani B . 2013. Non-LTR R2 element evolutionary patterns: phylogenetic incongruences, rapid radiation and the maintenance of multiple lineages. PLoS ONE 8 : e57076. [PubMed] [CrossRef]
15. Gladyshev EA,, Arkhipova IR . 2009. Rotifer rDNA-specific R9 retrotransposable elements generate an exceptionally long target site duplication upon insertion. Gene 448 : 145 150.[PubMed] [CrossRef]
16. Thompson BK,, Christensen SM . 2011. Independently derived targeting of 28S rDNA by A- and D-clade R2 retrotransposons. Mobile Genetic Elements 1 : 29 37.[PubMed] [CrossRef]
17. Fujiwara H . 2014. Mobile DNA III. [to be completed]
18. Burke WD,, Müller F,, Eickbush TH . 1995. R4, a non-LTR retrotransposon specific to the large subunit rRNA gene of nematodes. Nucleic Acids Res 23 : 4628 4634.[PubMed] [CrossRef]
19. Malik HS,, Eickbush TH . 2000. NeSL-1, an ancient lineage of site-specific non-LTR retrotransposons from Caenorhabditis elegans . Genetics 154 : 193 203.[PubMed]
20. Burke WD,, Singh D,, Eickbush TH . 2003. R5 retrotransposons insert into a family of infrequently transcribed 28S rRNA genes of Planaria. Mol Biol Evol 20 : 1260 1270.[PubMed] [CrossRef]
21. Burke WD,, Malik HS,, Rich SM,, Eickbush TH . 2002. Ancient lineages of non-LTR retrotransposons in the primitive eukaryote, Giardia lamblia . Mol Biol Evol 19 : 619 630.[PubMed] [CrossRef]
22. Kojima KK,, Fujiwara H . 2003. Evolution of target specificity in R1 clade non-LTR retrotransposons. Mol Biol Evol 20 : 351 361.[PubMed] [CrossRef]
23. Jakubczak JL,, Zenni MK,, Woodruff RC,, Eickbush TH . 1992. Turnover of R1 (Type I) and R2 (Type II) retrotransposable elements in the ribosomal DNA of Drosophila melanogaster . Genetics 131 : 129 142.[PubMed]
24. Pérez-González CE,, Eickbush TH . 2001. Dynamics of R1 and R2 Elements in the rDNA locus of Drosophila simulans . Genetics 158 : 1557 1567.[PubMed]
25. Pérez-González CE,, Eickbush TH . 2002. Rates of R1 and R2 retrotransposition and elimination from the rDNA locus of Drosophila melanogaster . Genetics 162 : 799 811.[PubMed]
26. Eickbush DG,, Eickbush TH . 1995. Vertical transmission of the retrotransposable elements R1 and R2 during the evolution of the Drosophila melanogaster species subgroup. Genetics 139 : 671 684.[PubMed]
27. Lathe WC III,, Eickbush TH . 1997. A single lineage of R2 retrotransposable elements is an active, evolutionarily stable component of the Drosophila rDNA locus. Mol Biol Evol 14 : 1232 1241.[PubMed] [CrossRef]
28. Burke WD,, Malik HS,, Lathe WC,, Eickbush TH . 1998. Are retrotransposons long term hitchhikers? Nature 239 : 141 142.[PubMed] [CrossRef]
29. Malik HS,, Burke WD,, Eickbush TH . 1999. The age and evolution of non-LTR retrotransposable elements. Mol Biol Evol 16 : 793 805.[PubMed] [CrossRef]
30. Burke WD,, Eickbush DG,, Xiong Y,, Jakubczak JL,, Eickbush TH . 1993. Sequence relationship of retrotransposable elements R1 and R2 within and between divergent insect species. Mol Biol Evol 10 : 163 185.[PubMed]
31. Stage DE,, Eickbush TE . 2010. Maintenance of multiple lineages of R1 and R2 retrotransposable elements in the ribosomal RNA gene loci of Nasonia . Insect Mol Biol 19( Suppl. 1) : 37 48.[PubMed] [CrossRef]
32. Hawley RS,, Marcus CH . 1989. Recombinational controls of rDNA redundancy in Drosophila . Annu Rev Genet 23 : 87 120.[PubMed] [CrossRef]
33. Zhang X,, Zhou J,, Eickbush TH . 2008. Rapid R2 retrotransposition leads to the loss of previously inserted copies via large deletions of the rDNA locus. Mol Biol Evol 25 : 229 237.[PubMed] [CrossRef]
34. Hollocher H,, Templeton AR . 1994. The molecular through ecological genetics of abnormal abdomen in Drosophila mercatorum. VI. The non-neutrality of the Y chromosome rDNA polymorphism. Genetics 136 : 1373 1384.[PubMed]
35. Malik HS,, Eickbush TH . 1999. Retrotransposable elements R1 and R2 in the rDNA units of Drosophila mercatorum: abnormal abdomen revisited. Genetics 151 : 653 665.[PubMed]
36. Xiong Y,, Eickbush TH . 1988. Functional expression of a sequence-specific endonuclease encoded by the retrotransposon R2Bm. Cell 55 : 235 246.[PubMed] [CrossRef]
37. Luan DD,, Korman MH,, Jakubczak JL,, Eickbush TH . 1993. Reverse transcription of R2Bm RNA is primed by a nick at the chromosomal target site: a mechanism for non-LTR retrotransposition. Cell 72 : 595 605.[PubMed] [CrossRef]
38. Craigie R, . 2002. Retroviral DNA integration, p 613 630. In Craig NL,, Craige R,, Gellert M,, Lambowitz AM (ed), Mobile DNA 11. ASM Press, Washington, DC.
39. Voytas DF,, Boeke JD, . 2002. Ty1 and Ty5 of Saccharomyces cerevisiae , p 631 662. In Craig NL,, Craige R,, Gellert M,, Lambowitz AM (ed), Mobile DNA 11. ASM Press, Washington, DC.
40. Eickbush TH, . 2002. R2 and related site-specific non-long terminal repeat retrotransposons, p 813 835. In Craig NL,, Craige R,, Gellert M,, Lambowitz AM (ed), Mobile DNA 11. ASM Press, Washington, DC.
41. Luan DD,, Eickbush TH . 1995. RNA template requirements for target DNA-primed reverse transcription by the R2 retrotransposable element. Mol Cell Biol 15 : 3882 3891.[PubMed]
42. Luan DD,, Eickbush TH . 1996. Downstream 28S gene sequences on the RNA template affect the choice of primer and the accuracy of initiation by the R2 reverse transcriptase. Mol Cell Biol 16 : 4726 4734.[PubMed]
43. Bibillo A,, Eickbush TH . 2002. The reverse transcriptase of the R2 non-LTR retrotransposon: continuous synthesis of cDNA on non-continuous RNA templates. J Mol Biol 316 : 459 473.[PubMed] [CrossRef]
44. Bibillo A,, Eickbush TH . 2002. High processivity of the reverse transcriptase from a non-long terminal repeat retrotransposon. J Biol Chem 277 : 34836 34845.[PubMed] [CrossRef]
45. Kurzynska-Kokorniak A,, Jamburuthugoda VK,, Bibillo A,, Eickbush TH . 2007. DNA-directed DNA polymerase and strand displacement activity of the reverse transcriptase encoded by the R2 retrotransposon. J Mol Biol 374 : 322 333.[PubMed] [CrossRef]
46. Bibillo A,, Eickbush TH . 2004. End-to-end template jumping by the reverse transcriptase encoded by the R2 retrotransposon. J Biol Chem 279 : 14945 14953.[PubMed] [CrossRef]
47. Arnold JJ,, Cameron CE . 1999. Poliovirus RNA-dependent RNA polymerase (3Dpol) is sufficient for template switching in vitro. J Biol Chem 274 : 2706 2716.[PubMed] [CrossRef]
48. Chen B,, Lambowitz AM . 1997. De novo and DNA primer-mediated initiation of cDNA synthesis by the Mauriceville retroplasmid reverse transcriptase involve recognition of a 3′ CCA sequence. J Mol Biol 271 : 311 332.[PubMed] [CrossRef]
49. Mohr S,, Ghanem E,, Smith W,, Sheeter D,, Qin Y,, King O,, Polioudakis D,, Iyer VR,, Hunicke-Smith S,, Swamy S,, Kuersten S,, Lambowitz AM . 2013. Thermostable group II intron reverse transcriptase fusion proteins and their use in cDNA synthesis and next-generation RNA sequencing. RNA 19 : 958 970.[PubMed] [CrossRef]
50. Peliska JA,, Benkovic SJ . 1992. Mechanism of DNA strand transfer reactions catalyzed by HIV-1 reverse transcriptase. Science 258 : 1112 1118.[PubMed] [CrossRef]
51. Malik HS,, Eickbush TH . 2001. Phylogenetic analysis of Ribonuclease H domains suggests a late, chimeric origin of LTR retrotransposable elements and retroviruses. Genome Res 11 : 1187 1197.[PubMed] [CrossRef]
52. Kelleher CD,, Champoux JJ . 1998. Characterization of RNA strand displacement synthesis by Moloney Murine Leukemia virus reverse transcriptase. J Biol Chem 273 : 9976 9986.[PubMed] [CrossRef]
53. Lanciault C,, Champoux JJ . 2004. Single unpaired nucleotides facilitate HIV-1 reverse transcriptase displacement synthesis through duplex RNA. J Biol Chem 279 : 32252 32261.[PubMed] [CrossRef]
54. Yao J,, Truong DM,, Lambowitz AM . 2013. Genetic and biochemical assays reveal a key role for replication restart proteins in group II intron retrohoming. PLOS Genetics 9 : e1003469. [PubMed] [CrossRef]
55. Jamburuthugoda VK,, Eickbush TH . 2011. The reverse transcriptase encoded by the non-LTR retrotransposon R2 is as error-prone as that encoded by HIV-1. J Mol Biol 407 : 661 672.[PubMed] [CrossRef]
56. Kim B,, Ayran JC,, Sagar SG,, Adman ET,, Fuller SM,, Tran NH,, Horrigan J . 1999. New human immunodeficiency virus, type 1 reverse transcriptase (HIV-1 RT) mutants with increased fidelity of DNA synthesis. Accuracy, template binding, and processivity. J Biol Chem 274 : 27666 27673.[PubMed] [CrossRef]
57. Preston BD,, Poiesz BJ,, Loeb LA . 1988. Fidelity of HIV-1 reverse transcriptase. Science 242 : 1168 1171.[PubMed] [CrossRef]
58. Christensen S,, Eickbush TH . 2004. Footprint of the R2Bm protein on its target site before and after cleavage in the presence and absence of RNA. J Mol Biol 336 : 1035 1045.[PubMed] [CrossRef]
59. Christensen SM,, Eickbush TH . 2005. R2 target primed reverse transcription: ordered cleavage and polymerization steps by protein subunits asymmetrically bound to the target DNA. Mol Cell Biol 25 : 6617 6628.[PubMed] [CrossRef]
60. Christensen SM,, Ye J,, Eickbush TH . 2006. RNA from the 5′ end of the R2 retrotransposon controls R2 protein binding to and cleavage of its DNA target site. Proc Natl Acad Sci USA 104 : 17602 17607.[PubMed] [CrossRef]
61. Moran JV,, Holmes SE,, Naas TP,, DeBerardinis RJ,, Boeke JD,, Kazazian HH . 1996. High frequency retrotransposition in cultured mammalian cells. Cell 87 : 917 927.[PubMed] [CrossRef]
62. Christensen SM,, Bibillo A,, Eickbush TH . 2005. Role of the R2 element amino-terminal domain in the target-primed reverse transcription reaction. Nucleic Acids Res 33 : 6461 6468.[PubMed] [CrossRef]
63. Shivram H,, Cawley D,, Christensen SM . 2011. Targeting novel sites: the N-terminal DNA binding domain of non-LTR retrotransposons is an adaptable module that is implicated in changing site specificities. Mob Genet Elements 1 : 169 178.[PubMed] [CrossRef]
64. Jamburuthugoda VK,, Eickbush TH . 2014. Identification of RNA binding motifs in the R2 retrotransposon-encoded reverse transcriptase ( Nuc Acids Res, in press). [PubMed] [CrossRef]
65. Clements AP,, Singer MF . 1998. The human LINE-1 reverse transcriptase: effects of deletions outside the common reverse transcriptase domain. Nucleic Acids Res 26 : 3528 3535.[PubMed] [CrossRef]
66. Moran JV,, Gilbert N, . 2002. Mammalian LINE-1 retrotransposons and related elements, p 836 869. In Craig NL,, Craige R,, Gellert M,, Lambowitz AM (ed), Mobile DNA 11. ASM Press, Washington, DC.
67. Gu SQ,, Cui X,, Mou S,, Mohr S,, Yao J,, Lambowitz AM . 2010. Genetic identification of potential RNA-binding regions in a group II intron-encoded reverse transcriptase. RNA 16 : 732 747.[PubMed] [CrossRef]
68. Rouda S,, Skordalakes E . 2007. Structure of the RNA binding domain of telomerase: implications for RNA recognition and binding. Structure 15 : 1403 1412.[PubMed] [CrossRef]
69. Mitchell M,, Gillis A,, Futahashi M,, Fujiwara H,, Skordalakes E . 2010. Structural basis for telomerase catalytic subunit TERT binding to RNA template and telomeric DNA. Nat Struct Mol Biol 17 : 513 518.[PubMed] [CrossRef]
70. Xiong Y,, Eickbush TH . 1990. Origin and evolution of retroelements based upon their reverse transcriptase sequences. EMBO J 9 : 3353 3362.[PubMed]
71. Blocker FJ,, Mohr G,, Conlan LH,, Qi L,, Belfort M,, Lambowitz AM . 2005. Domain structure and three-dimensional model of a group II intron-encoded reverse transcriptase. RNA 11 : 14 28.[PubMed] [CrossRef]
72. Eickbush TH . 1997. Telomerase and retrotransposons: which came first? Science 277 : 911 912.[PubMed] [CrossRef]
73. Arkhipova IA,, Pyatkov KI,, Meselson M,, Evgenev MB . 2003. Retroelements containing introns in diverse invertebrate taxa. Nature Genetics 33 : 123 124.[PubMed] [CrossRef]
74. Eickbush DG,, Luan DD,, Eickbush TH . 2000. Integration of Bombyx mori R2 sequences into the 28S ribosomal DNA loci of D. melanogaster . Mol Cell Biol 20 : 213 223.[PubMed] [CrossRef]
75. Fujimoto H,, Hirukawa Y,, Tani H,, Matsuura Y,, Hashido K,, Tsuchida K,, Takada N,, Kobayashi M,, Maekawa H . 2004. Integration of the 5′ end of the retrotransposon, R2Bm, can be complemented by homologous recombination. Nucleic Acids Res 32 : 1555 1565.[PubMed] [CrossRef]
76. Eickbush DG,, Ye J,, Zhang X,, Burke WD,, Eickbush TH . 2008. Epigenetic regulation of retrotransposons within the nucleolus of Drosophila. Mol Cell Biol 28 : 6452 6461.[PubMed] [CrossRef]
77. George JA,, Eickbush TH . 1999. Conserved features at the 5′ end of Drosophila R2 retrotransposable elements: implications for transcription and translation. Insect Mol Biol 8 : 3 10.[PubMed] [CrossRef]
78. Eickbush DG,, Eickbush TH . 2003. Transcription of endogenous and exogenous R2 elements in the rDNA gene locus of Drosophila melanogaster . Mol Cell Biol 23 : 3825 3836.[CrossRef]
79. Eickbush DG,, Eickbush TH . 2010. R2 retrotransposons encode a self-cleaving ribozyme for processing from an rRNA co-transcript. Mol Cell Biol 30 : 3142 3150.[PubMed] [CrossRef]
80. Been MD,, Wickham GS . 1997. Self-cleaving ribozymes of hepatitis delta virus RNA. Eur J Biochem 247 : 741 753.[PubMed] [CrossRef]
81. Ferré-D’Amaré AR,, Zhou K,, Doudna JA . 1998. Crystal structure of a hepatitis delta virus ribozyme. Nature 395 : 567 574.[PubMed] [CrossRef]
82. Nehdi A,, Perreault J-P . 2006. Unbiased in vitro selection reveals the unique character of the self-cleaving antigenomic HDV RNA sequence. Nucleic Acids Res 34 : 584 592.[PubMed] [CrossRef]
83. Ruminski DJ,, Webb C-HT,, Riccitelli NJ,, Lupták A . 2012. Processing and translation initiation of non-long terminal repeat retrotransposons by hepatitis delta virus (HDV)-like self-cleaving ribozymes. J Biol Chem 286 : 41286 41295.[PubMed] [CrossRef]
84. Eickbush DG,, Burke WD,, Eickbush TH . 2013. Evolution of the R2 retrotransposon ribozyme and its self-cleavage site. PLoS One 8 : e66441. [PubMed] [CrossRef]
85. Webb C-H,, Riccitelli NJ,, Ruminski DJ,, Lupták A . 2009. Widespread occurrence of self-cleaving ribozymes. Science 326 : 953. [PubMed] [CrossRef]
86. Sánchez-Luque FJ,, López MC,, Macias F,, Alonso C,, Thomas MC . 2011. Identification of an hepatitis delta virus-like ribozyme at the mRNA 5′ end of the L1Tc retrotransposon from Trypanosoma cruzi . Nucleic Acids Res 39 : 8065 8077.[PubMed] [CrossRef]
87. Stage DE,, Eickbush TH . 2009. Origin of nascent lineages and the mechanisms used to prime second-strand DNA synthesis in the R1 and R2 retrotransposons of Drosophila . Genome Biology 10 : R49. [PubMed] [CrossRef]
88. Eickbush DG,, Eickbush TH . 2012. R2 and R1/R1 hybrid non-autonomous retrotransposons derived by internal deletions of full-length elements. Mobile DNA 3 : 10. [PubMed] [CrossRef]
89. Ohshima K,, Okada N . 2005. SINEs and LINEs: symbionts of eukaryotic genomes with a common tail. Cytogenet Genome Res 110 : 475 490.[PubMed] [CrossRef]
90. Belancio VP,, Hedges DJ,, Deininger P . 2008. Mammalian non-LTR retrotransposons: for better or worse, in sickness and in health. Genome Res 18 : 343 358.[PubMed] [CrossRef]
91. Kierzek E,, Kierzek R,, Moss WN,, Christensen SM,, Eickbush TH,, Turner DH . 2008. Isoenergetic penta- and hexanucleotide microarray probing and chemical mapping provide a secondary structure model for an RNA element orchestrating R2 retrotransposon protein function. Nucleic Acids Res 36 : 1770 1782.[PubMed] [CrossRef]
92. Kierzek E,, Christensen SM,, Eickbush TE,, Kierzek R,, Turner DH,, Moss WN . 2009. Secondary structures for 5′ regions of R2 retrotransposon RNAs reveal a novel conserved pseudoknot and regions that evolve under different constraints. J Mol Biol 374 : 322 333.
93. Yang J,, Eickbush TH . 1998. RNA-induced changes in the activity of the endonuclease encoded by the R2 retrotransposable element. Mol Cell Biol 18 : 3455 3465.[PubMed]
94. George JA,, Burke WD,, Eickbush TH . 1996. Analysis of the 5′ junctions of R2 insertions with the 28S gene: implications for non-LTR retrotransposition. Genetics 142 : 853 863.[PubMed]
95. Ostertag EM,, Kazazian HH . 2001. Biology of mammalian L1 retrotransposons. Annu Rev Genet 35 : 501 538.[PubMed] [CrossRef]
96. Eickbush TH,, Eickbush DG . 2007. Finely orchestrated movements: evolution of the ribosomal RNA genes. Genetics 175 : 477 485.[PubMed] [CrossRef]
97. Stage DE,, Eickbush TH . 2007. Sequence variation within the rRNA gene loci of 12 Drosophila species. Genome Res 17 : 1888 1897.[PubMed] [CrossRef]
98. Zhang X,, Eickbush TH . 2005. Characterization of active R2 retrotransposition in the rDNA locus of Drosophila simulans . Genetics 170 : 195 205.[PubMed] [CrossRef]
99. Mingazzini V,, Luchetti A,, Mantovani B . 2011. R2 dynamics in Triops cancriformis (Bosc, 1801) (Crustacea, Branchiopoda, Notostraca): turnover rate and 28S concerted evolution. Heredity 106 : 567 575.[PubMed] [CrossRef]
100. Mackay TFC,, Lyman RF,, Jackson MS,, Terzian C,, Hill WG . 1992. Polygenic mutation in Drosophila melanogaster: estimates from divergence among inbred strains. Evolution 46 : 300 316.[CrossRef]
101. Pérez-González CE,, Burke WD,, Eickbush TH . 2003. R1 and R2 retrotransposition and deletion in the rDNA loci on the X and Y chromosomes of Drosophila melanogaster . Genetics 165 : 675 685.[PubMed]
102. Averbeck KT,, Eickbush TH . 2005. Monitoring the mode and tempo of concerted evolution in the Drosophila melanogaster rDNA locus. Genetics 171 : 1837 1846.[PubMed] [CrossRef]
103. Eickbush MT,, Eickbush TH . 2011. Retrotransposition of R2 elements in somatic nuclei during the early development of Drosophila. Mobile DNA 2 : 11. [PubMed] [CrossRef]
104. Long EO,, Dawid IB . 1979. Expression of ribosomal DNA insertions in Drosophila melanogaster . Cell 18 : 1185 1196.[PubMed] [CrossRef]
105. Kidd SJ,, Glover DM . 1981. D. melanogaster ribosomal DNA containing type II insertions is variably transcribed in different strains and tissues. J Mol Biol 151 : 645 662.[PubMed] [CrossRef]
106. Ye J,, Eickbush TH . 2006. Chromatin structure and transcription of the R1- and R2-inserted rRNA genes of Drosophila melanogaster . Mol Cell Biol 23 : 8781 8790.[PubMed] [CrossRef]
107. Jamrich M,, Miller OL . 1984. The rare transcripts of interrupted rDNA genes in Drosophila melanogaster are processed or degraded during synthesis. EMBO J 3 : 1541 1545.[PubMed]
108. Conconi A,, Widmer RM,, Koller T,, Sogo JM . 1989. Two different chromatin structures coexist in ribosomal RNA genes throughout the cell cycle. Cell 57 : 753 761.[PubMed] [CrossRef]
109. Conconi A,, Sogo JM,, Ryan CA . 1992. Ribosomal gene clusters are uniquely proportioned between open and closed chromatin structures in both tomato leaf cells and exponentially growing suspension cultures. Proc Natl Acad Sci USA 89 : 5256 5260.[PubMed] [CrossRef]
110. Dammann R,, Lucchini R,, Koller T,, Sogo JM . 1993. Chromatin structures and transcription of rDNA in yeast Saccharomyces cerevisiae . Nucleic Acids Res 21 : 2331 2338.[PubMed] [CrossRef]
111. McKnight SL,, Miller OL . 1976. Ultrastructural patterns of RNA synthesis during early embryogenesis of Drosophila melanogaster . Cell 8 : 305 319.[PubMed] [CrossRef]
112. Tucker S,, Vitins A,, Pikaard CS . 2010. Nucleolar dominance and ribosomal RNA gene silencing. Curr Opin Cell Biol 22 : 351 356.[PubMed] [CrossRef]
113. Zhou J,, Sackton TB,, Martinsen L,, Lemos B,, Eickbush TH,, Hartl DL . 2012. Y chromosome mediates ribosomal DNA silencing and modulates the chromatin state in Drosophila. Proc Natl Acad Sci USA 109 : 9941 9946.[PubMed] [CrossRef]
114. Greil F,, Ahmad K . 2012. Nucleolar dominance of the Y chromosome in Drosophila melanogaster . Genetics 191 : 1119 1128.[PubMed] [CrossRef]
115. Paredes S,, Branco AT,, Hartl DL,, Maggert KA,, Lemos B . 2011. Ribosomal DNA deletions modulate genome-wide gene expression: “rDNA-sensitive” genes and natural variation. PLoS Genetics 7 : e1001376. [PubMed] [CrossRef]
116. Paredes S,, Maggert KA . 2009. Expression of I-CreI endonuclease generates deletions within the rDNA of Drosophila. Genetics 181 : 1661 1671.[PubMed] [CrossRef]
117. Zhou J,, Eickbush TH . 2009. The pattern of R2 retrotransposon activity in natural populations of Drosophila simulans reflects the dynamic nature of the rDNA locus. PLoS Genetics 5 : e1000386. [PubMed] [CrossRef]
118. Zhou J,, Eickbush MT,, Eickbush TH . 2013. A population genetic model for the maintenance of R2 retrotransposons in rRNA gene loci. PLoS Genetics 8 : e1003179. [PubMed] [CrossRef]
119. Girard A,, Hannon GJ . 2008. Conserved themes in small-RNA-mediated transposon control. Trends Cell Biol 18 : 136 148.[PubMed] [CrossRef]
120. Senti K-A,, Brennecke J . 2010. The piRNA pathway: a fly’s perspective on the guardian of the genome. Trends in Genetics 26 : 499 509.[PubMed] [CrossRef]
121. Ghesini S,, Luchetti A,, Marini M,, Mantovani B . 2011. The non-LTR retrotransposon R2 in termites (Insecta, Isoptera): characterization and dynamics. J Mol Evol 72 : 296 305.[PubMed] [CrossRef]
122. Montiel EE,, Cabrero J,, Ruiz-Estévez M,, Burke WD,, Eickbush TH,, Camacho JPM,, López-León MD . 2014. Preferential occupancy of R2 retroelements on the B chromosome of the grasshopper Eyprepocnemis plorans . [PubMed] [CrossRef]
123. Ohta T . 1980. Evolution and variation of multigene families. Springer-Verlag, Berlin/Heidelberg, Germany/New York. [CrossRef]
124. Ohta T,, Dover GA . 1983. Population genetics of multigene families that are dispersed into two or more chromosomes. Proc Natl Acad Sci USA 80 : 4079 4083.[CrossRef]
125. Lyckegaard EMS,, Clark AG . 1991. Evolution of ribosomal RNA gene copy number on the sex chromosomes of Drosophila melanogaster . Mol Biol Evol 8 : 458 474.[PubMed]
126. Zhang X,, Eickbush MT,, Eickbush TH . 2008. Role of recombination in the long-term retention of transposable elements in rRNA gene loci. Genetics 180 : 1617 1626.[PubMed] [CrossRef]
127. Aguilera A,, Gómez-González B . 2008. Genome instability: a mechanistic view of its causes and consequences. Nature Rev Genetics 9 : 204 217.[PubMed] [CrossRef]
128. Voelket-Meiman K,, Keil RL,, Roeder GS . 1987. Recombination-stimulating sequences in yeast ribosomal DNA correspond to sequences regulating transcription by RNA polymerase I. Cell 48 : 1071 1079.[PubMed] [CrossRef]

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error