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EcoSal Plus

Domain 4:

Synthesis and Processing of Macromolecules

Modified Nucleosides of Ribosomal RNA

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  • Authors: James Ofengand1, and Mark Del Campo2
  • Editor: Susan T. Lovett3
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, Miami, FL 33136; 2: Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, Miami, FL 33136; 3: Brandeis University, Waltham, MA
  • Received 19 May 2004 Accepted 08 August 2004 Published 29 December 2004
  • Address correspondence to Mark Del Campo mdelcamp_mail@yahoo.com
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  • Abstract:

    The modified nucleosides of RNA are chemically altered versions of the standard A, G, U, and C nucleosides. This review reviews the nature and location of the modified nucleosides of rRNA, the enzymes that form them, and their known and/or putative functional role. There are seven Ψ (pseudouridines) synthases to make the 11 pseudouridines in rRNA. There is disparity in numbers because RluC and RluD each make 3 pseudouridines. Crystal structures have shown that the Ψ synthase domain is a conserved fold found only in all five families of Ψ synthases. The conversion of uridine to Ψ has no precedent in known metabolic reactions. Other enzymes are known to cleave the glycosyl bond but none carry out rotation of the base and rejoining to the ribose while still enzyme bound. Ten methyltransferases (MTs) are needed to make all the methylated nucleosides in 16S RNA, and 14 are needed for 23S RNA. Biochemical studies indicate that the modes of substrate recognition are idiosyncratic for each Ψ synthase since no common mode of recognition has been detected in studies of the seven synthases. Eight of the 24 expected MTs have been identified, and six crystal structures have been determined. Seven of the MTs and five of the structures are class I MTs with the appropriate protein fold plus unique appendages for the Ψ synthases. The remaining MT, RlmB, has the class IV trefoil knot fold.

  • Citation: Ofengand J, Del Campo M. 2004. Modified Nucleosides of Ribosomal RNA, EcoSal Plus 2004; doi:10.1128/ecosalplus.4.6.1

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/content/journal/ecosalplus/10.1128/ecosalplus.4.6.1
2004-12-29
2017-12-14

Abstract:

The modified nucleosides of RNA are chemically altered versions of the standard A, G, U, and C nucleosides. This review reviews the nature and location of the modified nucleosides of rRNA, the enzymes that form them, and their known and/or putative functional role. There are seven Ψ (pseudouridines) synthases to make the 11 pseudouridines in rRNA. There is disparity in numbers because RluC and RluD each make 3 pseudouridines. Crystal structures have shown that the Ψ synthase domain is a conserved fold found only in all five families of Ψ synthases. The conversion of uridine to Ψ has no precedent in known metabolic reactions. Other enzymes are known to cleave the glycosyl bond but none carry out rotation of the base and rejoining to the ribose while still enzyme bound. Ten methyltransferases (MTs) are needed to make all the methylated nucleosides in 16S RNA, and 14 are needed for 23S RNA. Biochemical studies indicate that the modes of substrate recognition are idiosyncratic for each Ψ synthase since no common mode of recognition has been detected in studies of the seven synthases. Eight of the 24 expected MTs have been identified, and six crystal structures have been determined. Seven of the MTs and five of the structures are class I MTs with the appropriate protein fold plus unique appendages for the Ψ synthases. The remaining MT, RlmB, has the class IV trefoil knot fold.

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Figures

Image of Figure 1
Figure 1

Ψ, 5−ribosyluracil (pseudouridine); mΨ, 3-methylpseudouridine; mU, 3-methyluridine; mU, 5-methyluridine; hU, 5,6-dihydrouridine; mC, N-methylcytidine; mC, 5-methylcytidine; Nm, 2′-OCH-N (N = A, G, U, or C); mA, 2-methyladenosine; mA, N-methyladenosine; m A, N-dimethyladenosine; mG, 1-methylguanosine; mG, N-methylguanosine; mG, 7-methylguanosine.

Citation: Ofengand J, Del Campo M. 2004. Modified Nucleosides of Ribosomal RNA, EcoSal Plus 2004; doi:10.1128/ecosalplus.4.6.1
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Figure 2

The secondary structure is modified from the Comparative RNA Web Site (http://www.rna.icmb.utexas.edu/). Modified nucleoside positions are as indicated.

Citation: Ofengand J, Del Campo M. 2004. Modified Nucleosides of Ribosomal RNA, EcoSal Plus 2004; doi:10.1128/ecosalplus.4.6.1
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Figure 3

The secondary structure was obtained as in Fig. 2 and is shown with the modified nucleosides as indicated.

Citation: Ofengand J, Del Campo M. 2004. Modified Nucleosides of Ribosomal RNA, EcoSal Plus 2004; doi:10.1128/ecosalplus.4.6.1
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Figure 4

(A) View from the interface side of the ribosomal subunit. (B) View in A rotated by 90°. The three-dimensional structure of the 16S RNA of the 30S ribosome of ( 54 ; Protein Data Bank [PDB] entry 1J5E) is shown with all proteins removed and the phosphodiester backbone represented by a continuous line. Ψ residues are shown as 6-Å-diameter red spheres. Methylated nucleosides are shown as 6-Å-diameter green spheres irrespective of whether they are purine or pyrimidine derived or base methylated versus ribose methylated. All spheres are centered on the glycosyl N of the base. The identifying numbers are listed in Table 1 and 2 .

Citation: Ofengand J, Del Campo M. 2004. Modified Nucleosides of Ribosomal RNA, EcoSal Plus 2004; doi:10.1128/ecosalplus.4.6.1
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Figure 5

(A) View from the interface side of the ribosomal subunit. (B) View in panel A rotated by 90°. The three-dimensional structure of the 23S RNA of the 50S ribosome of ( 55 ; PDB entry 1NKW) is shown the same way as in Fig. 4 . Ψ and methylated nucleosides are denoted as in Fig. 4 . Dihydrouridine and the unidentified modified C2501 are shown as a light blue and yellow 6-Å sphere, respectively. All spheres are centered on the glycosyl N of the base. Residue 2057 (cyan sphere marked by black triangle), 2058 and 2059 (cyan spheres), 2062 (orange sphere), 2609 (orange sphere marked by black triangle), and 2611 (black sphere) are all located at the interface entrance to the exit tunnel ( 56 , 57 ). These spheres are 3 Å in diameter to conserve space.

Citation: Ofengand J, Del Campo M. 2004. Modified Nucleosides of Ribosomal RNA, EcoSal Plus 2004; doi:10.1128/ecosalplus.4.6.1
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Figure 6

Five of the synthases have an N-terminal domain similar to the RNA-binding domain of ribosomal protein S4 (grey bar). The five motifs described by Del Campo et al. ( 20 ) are indicated with different colored bars matching the colored ribbon segments in Fig. 8 . The S4 domain secondary structure (above) is from the crystal structure of RsuA ( 18 ; PDB entry 1KSK). The Ψ synthase domain secondary structure (above) is from the crystal structures of RsuA and RluD ( 20 ; PDB entry 1QYU) by using those elements consistent with both structures. Conserved residues are shown in bold face with conserved active-site residues highlighted in yellow and other identical residues highlighted in light blue. Numbers to the left of each line denote the sequence position of the first residue shown. Dashes indicate gaps in sequence, and numbers in parentheses indicate the number of residues that are not shown in the alignment.

Citation: Ofengand J, Del Campo M. 2004. Modified Nucleosides of Ribosomal RNA, EcoSal Plus 2004; doi:10.1128/ecosalplus.4.6.1
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Figure 7

(A) Ribbon cartoon of RsuA ( 18 ; PDB entry 1KSK) in blue superposed onto RluD ( 20 ; PDB entry 1QYU) in orange using DALI ( 63 ). Nonoverlapping domains are labeled. (B) Superposed side chains (starting at the C) from the five conserved active-site residues of RluD and RsuA (highlighted in yellow in Fig. 6 ). The N, C, C, C, and O atoms of all five residues from RsuA were superposed onto the equivalent five residues of RluD using LSQMAN ( 64 ). Colors are the same as in panel A. The figure was generated with PyMOL ( 65 ).

Citation: Ofengand J, Del Campo M. 2004. Modified Nucleosides of Ribosomal RNA, EcoSal Plus 2004; doi:10.1128/ecosalplus.4.6.1
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Image of Figure 8
Figure 8

Ribbon cartoon of RluD is light gray. Motifs I, II, IIa, III, and IIIa are the same colors as the bars in Fig. 6 . The side chains of the five conserved active-site residues (highlighted yellow in Fig. 6 ) are shown in ball-and-stick representation and are the same color as the motif to which they belong. The figure was generated with PyMOL ( 65 ).

Reprinted with permission from reference 20 .

Citation: Ofengand J, Del Campo M. 2004. Modified Nucleosides of Ribosomal RNA, EcoSal Plus 2004; doi:10.1128/ecosalplus.4.6.1
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Tables

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Table 1

Pseudouridines in rRNA and the synthases that make them

Citation: Ofengand J, Del Campo M. 2004. Modified Nucleosides of Ribosomal RNA, EcoSal Plus 2004; doi:10.1128/ecosalplus.4.6.1
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Table 2

Other modified nucleosides in rRNA and their enzymes

Citation: Ofengand J, Del Campo M. 2004. Modified Nucleosides of Ribosomal RNA, EcoSal Plus 2004; doi:10.1128/ecosalplus.4.6.1
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Table 3

Effect of deletion of rRNA pseudouridine synthases on cell growth

Citation: Ofengand J, Del Campo M. 2004. Modified Nucleosides of Ribosomal RNA, EcoSal Plus 2004; doi:10.1128/ecosalplus.4.6.1

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