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Category: Microbial Genetics and Molecular Biology
Modified Nucleosides in Translation, Page 1 of 2
< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555818296/9781555811334_Chap27-1.gif /docserver/preview/fulltext/10.1128/9781555818296/9781555811334_Chap27-2.gifAbstract:
Cellular physiology is fundamentally dependent on the functions of translational apparatus, and these functions are dependent on modified nucleosides. This chapter examines the translational functions of modified nucleosides in the anticodon arm of tRNA. There are modifications at other positions within tRNA, but our knowledge of translational effects is limited to the modifications in the anticodon region. Emphasis is placed on the effects that the loss of specific modifications has on the activities of tRNA. Before considering the effects of modifications on translation, it is helpful to review certain aspects of the decoding process. Further work on the translational mechanism is needed to fully understand the roles of modified nucleosides in the important cellular process. The chapter discusses the effects of modified nucleosides at various positions in the anticodon arm. There are data on the translational effects of a subset of the modified nucleosides that occur within the anticodon arm. The chapter talks about a discussion of unmodified U34 because models for decoding by the modified forms are extended from those for unmodified U. Virtually all tRNAs contain modified nucleosides within the anticodon region, and it has become abundantly clear that they contribute to translation in a number of ways. The future looks very promising for the continued study and understanding of the roles that modified nucleosides play in the fundamentally important translational process.
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Schematic structure of the tRNA anticodon arm. The ribbon structure of yeast tRNAPhe is shown on the left. The anticodon arm (AC arm) is the bottom quarter of the molecule, and the anticodon nucleotides (AC) are indicated at the bottom. A detailed view of the AC arm is shown on the right. The stem includes the five base pairs on the top, and the loop contains seven nucleotides. The anticodon nucleotides are 36, 35, and 34, which read codon bases 1, 2, and 3, respectively. The U turn” in the backbone occurs between the highly conserved U33 and the 5′ end of the anticodon. All of the nucleotides discussed in the text are indicated. (Adapted from Saenger, 1984 .)
Schematic structure of the tRNA anticodon arm. The ribbon structure of yeast tRNAPhe is shown on the left. The anticodon arm (AC arm) is the bottom quarter of the molecule, and the anticodon nucleotides (AC) are indicated at the bottom. A detailed view of the AC arm is shown on the right. The stem includes the five base pairs on the top, and the loop contains seven nucleotides. The anticodon nucleotides are 36, 35, and 34, which read codon bases 1, 2, and 3, respectively. The U turn” in the backbone occurs between the highly conserved U33 and the 5′ end of the anticodon. All of the nucleotides discussed in the text are indicated. (Adapted from Saenger, 1984 .)
Examples of base pair geometries that may occur at the wobble position. On the left are representatives of the four structures predicted by Crick (1966) to function in decoding. For each base pair, the codon nucleotide is on the right and is fixed in the standard 3′-endo, A conformation (see the discussions in Li and Venclovas, 1992; Yokoyama and Nishimura, 1995 ). The anticodon nucleotide may assume a “wobble” conformation. The boldface brackets indicate the positions of the N-glycosidic bonds for the Watson–Crick base pairs. Anticodon nucleotide wobble deviations from Watson–Crick geometry are indicated by curved arrows. At the top left is the G:C base pair, which is representative of the Watson–Crick base pairs (G:C, C:G, A:U, U:A, and I:C), all of which are geometrically equivalent. Just below are the U:G and G:U base pairs, in which the anticodon bases are slightly shifted into the major and minor grooves, respectively. The I:U base pair is geometrically equivalent to the G:U base pair. At the bottom left is the “long wobble” I:A base pair. On the right are two hypothetical schemes for base pairing between uridines. At the top right is the “short wobble” conformation favored by Yokoyama and Nishimura (1995 ). This base pair requires a 2′-endo conformation for the anticodon uridine. At the bottom right is the conformation preferred by Lim (1995 ) in which a water molecule in the minor groove bridges between the uridine bases. This base pair does not require a 2′-endo conformation, but it does require a significant rotation of the anticodon base about the N-glycosidic bond (propeller twist). The propeller twist is not depicted in this two-dimensional diagram. (Adapted from Saenger, 1984 .)
Examples of base pair geometries that may occur at the wobble position. On the left are representatives of the four structures predicted by Crick (1966) to function in decoding. For each base pair, the codon nucleotide is on the right and is fixed in the standard 3′-endo, A conformation (see the discussions in Li and Venclovas, 1992; Yokoyama and Nishimura, 1995 ). The anticodon nucleotide may assume a “wobble” conformation. The boldface brackets indicate the positions of the N-glycosidic bonds for the Watson–Crick base pairs. Anticodon nucleotide wobble deviations from Watson–Crick geometry are indicated by curved arrows. At the top left is the G:C base pair, which is representative of the Watson–Crick base pairs (G:C, C:G, A:U, U:A, and I:C), all of which are geometrically equivalent. Just below are the U:G and G:U base pairs, in which the anticodon bases are slightly shifted into the major and minor grooves, respectively. The I:U base pair is geometrically equivalent to the G:U base pair. At the bottom left is the “long wobble” I:A base pair. On the right are two hypothetical schemes for base pairing between uridines. At the top right is the “short wobble” conformation favored by Yokoyama and Nishimura (1995 ). This base pair requires a 2′-endo conformation for the anticodon uridine. At the bottom right is the conformation preferred by Lim (1995 ) in which a water molecule in the minor groove bridges between the uridine bases. This base pair does not require a 2′-endo conformation, but it does require a significant rotation of the anticodon base about the N-glycosidic bond (propeller twist). The propeller twist is not depicted in this two-dimensional diagram. (Adapted from Saenger, 1984 .)
Frameshifting competes with normal translation at the RF2-programmed frameshift site. Shown is an example of an RF2 variant used to measure the relative rate of aa-tRNA selection at the leucine CUG codon. Prior to the frameshift (top) the peptidyl-tRNA is base paired to message CUU in the ribosomal Ρ site. The next triplet, CUG, is available for decoding in the A site. Normal translation occurs if tRNALeu binds productively at the A site, fixing the “0” reading frame. Alternatively, frameshifting occurs when the peptidyl-tRNA slips one nucleotide rightward onto UUC, fixing the “+1”reading frame. (For mechanistic details of the RF2-programmed frameshift, see Atkins and Gesteland, 1995 ; Curran and Yarus, 1988 ; Farabaugh, 1996 ; Gesteland and Atkins, 1996 ; and Weiss et al., 1988. )
Frameshifting competes with normal translation at the RF2-programmed frameshift site. Shown is an example of an RF2 variant used to measure the relative rate of aa-tRNA selection at the leucine CUG codon. Prior to the frameshift (top) the peptidyl-tRNA is base paired to message CUU in the ribosomal Ρ site. The next triplet, CUG, is available for decoding in the A site. Normal translation occurs if tRNALeu binds productively at the A site, fixing the “0” reading frame. Alternatively, frameshifting occurs when the peptidyl-tRNA slips one nucleotide rightward onto UUC, fixing the “+1”reading frame. (For mechanistic details of the RF2-programmed frameshift, see Atkins and Gesteland, 1995 ; Curran and Yarus, 1988 ; Farabaugh, 1996 ; Gesteland and Atkins, 1996 ; and Weiss et al., 1988. )
Summary of the effects of modified nucleosides on translation
Summary of the effects of modified nucleosides on translation