Loss of rRNA modifications in the decoding center of the ribosome impairs translation and strongly delays pre-rRNA processing

Liang, Xiaojing; Liu, Qing; Fournier, Maurille J.

doi:10.1261/rna.1724409

Cited by 199 publications

(204 citation statements)

References 47 publications

(67 reference statements)

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“…The box H/ACA snoRNPs catalyze pseudouridylation at 44 sites on the rRNA, while the box C/D snoRNPs catalyze 29-O-ribose methylation at 67 sites (Balakin et al 1996;Kiss-Laszlo et al 1996;Ganot et al 1997;X. H. Liang et al 2009;Watkins and Bohnsack 2012) (Figure 6).…”

Section: Pre-rrna Processing Can Occur Cotranscriptionallymentioning

confidence: 99%

Ribosome Biogenesis in the YeastSaccharomyces cerevisiae

2013

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Ribosomes are highly conserved ribonucleoprotein nanomachines that translate information in the genome to create the proteome in all cells. In yeast these complex particles contain four RNAs (.5400 nucleotides) and 79 different proteins. During the past 25 years, studies in yeast have led the way to understanding how these molecules are assembled into ribosomes in vivo. Assembly begins with transcription of ribosomal RNA in the nucleolus, where the RNA then undergoes complex pathways of folding, coupled with nucleotide modification, removal of spacer sequences, and binding to ribosomal proteins. More than 200 assembly factors and 76 small nucleolar RNAs transiently associate with assembling ribosomes, to enable their accurate and efficient construction. Following export of preribosomes from the nucleus to the cytoplasm, they undergo final stages of maturation before entering the pool of functioning ribosomes. Elaborate mechanisms exist to monitor the formation of correct structural and functional neighborhoods within ribosomes and to destroy preribosomes that fail to assemble properly. Studies of yeast ribosome biogenesis provide useful models for ribosomopathies, diseases in humans that result from failure to properly assemble ribosomes. TABLE OF CONTENTS Abstract 643Introduction 644

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Section: Pre-rrna Processing Can Occur Cotranscriptionallymentioning

confidence: 99%

Ribosome Biogenesis in the YeastSaccharomyces cerevisiae

2013

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“…For example, a cluster of pseudouridines in the A-site finger of the large ribosomal subunit in yeast positively affects translation efficiency and fidelity (PieknaPrzybylska et al 2008;Baudin-Baillieu et al 2009). Also, simultaneous removal of several modifications in the 18S rRNA decoding center results in lower amino acid incorporation rates, reduced translational fidelity, and delayed 18S rRNA synthesis (Baudin-Baillieu et al 2009;Liang et al 2009). In addition, function of the peptidyl-transferase center (PTC) of the large ribosomal subunit seems also to be optimized by rRNA modifications.…”

Section: Introductionmentioning

confidence: 99%

A cluster of methylations in the domain IV of 25S rRNA is required for ribosome stability

Gigova

Duggimpudi

Pollex

et al. 2014

RNA

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In all three domains of life ribosomal RNAs are extensively modified at functionally important sites of the ribosome. These modifications are believed to fine-tune the ribosome structure for optimal translation. However, the precise mechanistic effect of modifications on ribosome function remains largely unknown. Here we show that a cluster of methylated nucleotides in domain IV of 25S rRNA is critical for integrity of the large ribosomal subunit. We identified the elusive cytosine-5 methyltransferase for C2278 in yeast as Rcm1 and found that a combined loss of cytosine-5 methylation at C2278 and ribose methylation at G2288 caused dramatic ribosome instability, resulting in loss of 60S ribosomal subunits. Structural and biochemical analyses revealed that this instability was caused by changes in the structure of 25S rRNA and a consequent loss of multiple ribosomal proteins from the large ribosomal subunit. Our data demonstrate that individual RNA modifications can strongly affect structure of large ribonucleoprotein complexes.

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“…Post-transcriptional modifications in spliceosomal small nuclear RNAs (snRNAs) and ribosomal RNAs (rRNAs) are essential for spliceosome assembly and splicing competency (Yu et al 1998;Donmez et al 2004;Yu 2004, 2007;Yang et al 2005;Karijolich and Yu 2010) as well as for the assembly of functional ribosomal subunits and the efficiency and fidelity of translation (Lapeyre 2005;Liang et al 2007Liang et al , 2009Esguerra et al 2008;Jack et al 2011). Two common alterations in these RNAs, namely, pseudouridylation and 2 ′ -O-methylation, are usually mediated by the so-called modification guide RNAs, the box H/ACA and box C/D RNAs, respectively.…”

Section: Introductionmentioning

confidence: 99%

Novel small Cajal-body-specific RNAs identified in Drosophila: probing guide RNA function

Deryusheva

Gall

2013

RNA

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The spliceosomal small nuclear RNAs (snRNAs) are modified post-transcriptionally by introduction of pseudouridines and 2 ′ -Omethyl modifications, which are mediated by box H/ACA and box C/D guide RNAs, respectively. Because of their concentration in the nuclear Cajal body (CB), these guide RNAs are known as small CB-specific (sca) RNAs. In the cell, scaRNAs are associated with the WD-repeat protein WDR79. We used coimmunoprecipitation with WDR79 to recover seven new scaRNAs from Drosophila cell lysates. We demonstrated concentration of these new scaRNAs in the CB by in situ hybridization, and we verified experimentally that they can modify their putative target RNAs. Surprisingly, one of the new scaRNAs targets U6 snRNA, whose modification is generally assumed to occur in the nucleolus, not in the CB. Two other scaRNAs have dual guide functions, one for an snRNA and one for 28S rRNA. Again, the modification of 28S rRNA is assumed to take place in the nucleolus. These findings suggest that canonical scaRNAs may have functions in addition to their established role in modifying U1, U2, U4, and U5 snRNAs. We discuss the likelihood that processing by scaRNAs is not limited to the CB.

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Loss of rRNA modifications in the decoding center of the ribosome impairs translation and strongly delays pre-rRNA processing

Cited by 199 publications

References 47 publications

Ribosome Biogenesis in the YeastSaccharomyces cerevisiae

Ribosome Biogenesis in the YeastSaccharomyces cerevisiae

A cluster of methylations in the domain IV of 25S rRNA is required for ribosome stability

Novel small Cajal-body-specific RNAs identified in Drosophila: probing guide RNA function

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