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The human 18S rRNA base methyltransferases DIMT1L and WBSCR22-TRMT112 but not rRNA modification are required for ribosome biogenesis.

Zorbas C, Nicolas E, Wacheul L, Huvelle E, Heurgué-Hamard V, Lafontaine DL - Mol. Biol. Cell (2015)

Bottom Line: We conclude that a quality control mechanism has been conserved from yeast to human by which binding of a methyltransferase to nascent pre-rRNAs is a prerequisite to processing, so that all cleaved RNAs are committed to faithful modification.We further report that 18S rRNA dimethylation is nuclear in human cells, in contrast to yeast, where it is cytoplasmic.Yeast and human ribosome biogenesis thus have both conserved and distinctive features.

View Article: PubMed Central - PubMed

Affiliation: RNA Molecular Biology, Fonds de la Recherche Scientifique (FRS/FNRS), Université Libre de Bruxelles, B-6041 Charleroi-Gosselies, Belgium.

No MeSH data available.


Related in: MedlinePlus

The 18S rRNA m7G and  modifications are conserved in S. cerevisiae and Homo sapiens. (A) Secondary structure of the 18S rRNA. The insets illustrate conservation of rRNA sequence and secondary structure near the N7-methylguanosine (m7G) modification introduced by Bud23-Trm112 in yeast and WBSCR22-TRMT112 in humans and in the vicinity of the two N6,N6-dimethyladenosines  synthesized by Dim1 in yeast and DIMT1L in humans. Modified nucleotide positions are highlighted in red. The 5′, central (C), 3′ major (3′ M), and 3′ minor (3′ m) domains are indicated. (B) Three-dimensional representation of the yeast small subunit (model based on Protein Data Bank entry 3U5B) with posttranscriptional modifications and functional sites highlighted. The decoding site (DCS, in cyan) at the base of helix 44 (in anthracite) and the mRNA entry (green circle) and exit (red circle) sites are indicated. Residues shown as green and red spheres are 2′-O methylated or pseudouridylated, respectively. Bd, body; Bk, beak; H, head; Lf, left foot; Nk, neck; Pt; platform, Rf, right foot; Sh, shoulder.
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Figure 1: The 18S rRNA m7G and modifications are conserved in S. cerevisiae and Homo sapiens. (A) Secondary structure of the 18S rRNA. The insets illustrate conservation of rRNA sequence and secondary structure near the N7-methylguanosine (m7G) modification introduced by Bud23-Trm112 in yeast and WBSCR22-TRMT112 in humans and in the vicinity of the two N6,N6-dimethyladenosines synthesized by Dim1 in yeast and DIMT1L in humans. Modified nucleotide positions are highlighted in red. The 5′, central (C), 3′ major (3′ M), and 3′ minor (3′ m) domains are indicated. (B) Three-dimensional representation of the yeast small subunit (model based on Protein Data Bank entry 3U5B) with posttranscriptional modifications and functional sites highlighted. The decoding site (DCS, in cyan) at the base of helix 44 (in anthracite) and the mRNA entry (green circle) and exit (red circle) sites are indicated. Residues shown as green and red spheres are 2′-O methylated or pseudouridylated, respectively. Bd, body; Bk, beak; H, head; Lf, left foot; Nk, neck; Pt; platform, Rf, right foot; Sh, shoulder.

Mentions: Although the precise involvement of rRNA base modifications in translation is not fully understood, their conservation and conspicuous presence at functional sites suggest that they are important. The modification (yeast numbering), in the 18S rRNA 3′ minor domain, is on the apical loop of a highly conserved hairpin (helix 45), which folds near the decoding site in the three-dimensional structure of the ribosome (Figure 1). The m7G1575 modification, in the 18S rRNA 3′ major domain, is at a ridge forming a steric block between the P-site and E-site tRNAs at the back of the small subunit head (Figure 1). The modification is one of the most highly conserved rRNA base modifications (van Knippenberg, 1986; Rife, 2009). With a few exceptions, including organellar ribosomes of Euglena gracilis and Saccharomyces cerevisiae, it is present on all ribosomes inspected to date in all three kingdoms of life (van Knippenberg, 1986; Rife, 2009). In a recent phylogenetic analysis focused on Mollicutes parasitic bacteria, which has undergone massive genome reduction during evolution, investigators defined a minimal set of core ribosome biogenesis and translation factors (Grosjean et al., 2014). They showed that KsgA (the bacterial homologue of Dim1) is part of this set. This is significant because KsgA is one of the very few rRNA modification enzymes to have been retained during Mollicutes genomic erosion (Grosjean et al., 2014). This supports the notion that KsgA is primordial and was presumably present in the last common ancestor (Rife, 2009). The m7G1575 modification, on the other hand, is conserved throughout eukaryotes but is not found in bacteria or Archaea.


The human 18S rRNA base methyltransferases DIMT1L and WBSCR22-TRMT112 but not rRNA modification are required for ribosome biogenesis.

Zorbas C, Nicolas E, Wacheul L, Huvelle E, Heurgué-Hamard V, Lafontaine DL - Mol. Biol. Cell (2015)

The 18S rRNA m7G and  modifications are conserved in S. cerevisiae and Homo sapiens. (A) Secondary structure of the 18S rRNA. The insets illustrate conservation of rRNA sequence and secondary structure near the N7-methylguanosine (m7G) modification introduced by Bud23-Trm112 in yeast and WBSCR22-TRMT112 in humans and in the vicinity of the two N6,N6-dimethyladenosines  synthesized by Dim1 in yeast and DIMT1L in humans. Modified nucleotide positions are highlighted in red. The 5′, central (C), 3′ major (3′ M), and 3′ minor (3′ m) domains are indicated. (B) Three-dimensional representation of the yeast small subunit (model based on Protein Data Bank entry 3U5B) with posttranscriptional modifications and functional sites highlighted. The decoding site (DCS, in cyan) at the base of helix 44 (in anthracite) and the mRNA entry (green circle) and exit (red circle) sites are indicated. Residues shown as green and red spheres are 2′-O methylated or pseudouridylated, respectively. Bd, body; Bk, beak; H, head; Lf, left foot; Nk, neck; Pt; platform, Rf, right foot; Sh, shoulder.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Figure 1: The 18S rRNA m7G and modifications are conserved in S. cerevisiae and Homo sapiens. (A) Secondary structure of the 18S rRNA. The insets illustrate conservation of rRNA sequence and secondary structure near the N7-methylguanosine (m7G) modification introduced by Bud23-Trm112 in yeast and WBSCR22-TRMT112 in humans and in the vicinity of the two N6,N6-dimethyladenosines synthesized by Dim1 in yeast and DIMT1L in humans. Modified nucleotide positions are highlighted in red. The 5′, central (C), 3′ major (3′ M), and 3′ minor (3′ m) domains are indicated. (B) Three-dimensional representation of the yeast small subunit (model based on Protein Data Bank entry 3U5B) with posttranscriptional modifications and functional sites highlighted. The decoding site (DCS, in cyan) at the base of helix 44 (in anthracite) and the mRNA entry (green circle) and exit (red circle) sites are indicated. Residues shown as green and red spheres are 2′-O methylated or pseudouridylated, respectively. Bd, body; Bk, beak; H, head; Lf, left foot; Nk, neck; Pt; platform, Rf, right foot; Sh, shoulder.
Mentions: Although the precise involvement of rRNA base modifications in translation is not fully understood, their conservation and conspicuous presence at functional sites suggest that they are important. The modification (yeast numbering), in the 18S rRNA 3′ minor domain, is on the apical loop of a highly conserved hairpin (helix 45), which folds near the decoding site in the three-dimensional structure of the ribosome (Figure 1). The m7G1575 modification, in the 18S rRNA 3′ major domain, is at a ridge forming a steric block between the P-site and E-site tRNAs at the back of the small subunit head (Figure 1). The modification is one of the most highly conserved rRNA base modifications (van Knippenberg, 1986; Rife, 2009). With a few exceptions, including organellar ribosomes of Euglena gracilis and Saccharomyces cerevisiae, it is present on all ribosomes inspected to date in all three kingdoms of life (van Knippenberg, 1986; Rife, 2009). In a recent phylogenetic analysis focused on Mollicutes parasitic bacteria, which has undergone massive genome reduction during evolution, investigators defined a minimal set of core ribosome biogenesis and translation factors (Grosjean et al., 2014). They showed that KsgA (the bacterial homologue of Dim1) is part of this set. This is significant because KsgA is one of the very few rRNA modification enzymes to have been retained during Mollicutes genomic erosion (Grosjean et al., 2014). This supports the notion that KsgA is primordial and was presumably present in the last common ancestor (Rife, 2009). The m7G1575 modification, on the other hand, is conserved throughout eukaryotes but is not found in bacteria or Archaea.

Bottom Line: We conclude that a quality control mechanism has been conserved from yeast to human by which binding of a methyltransferase to nascent pre-rRNAs is a prerequisite to processing, so that all cleaved RNAs are committed to faithful modification.We further report that 18S rRNA dimethylation is nuclear in human cells, in contrast to yeast, where it is cytoplasmic.Yeast and human ribosome biogenesis thus have both conserved and distinctive features.

View Article: PubMed Central - PubMed

Affiliation: RNA Molecular Biology, Fonds de la Recherche Scientifique (FRS/FNRS), Université Libre de Bruxelles, B-6041 Charleroi-Gosselies, Belgium.

No MeSH data available.


Related in: MedlinePlus