Tuning the ribosome: The influence of rRNA modification on eukaryotic ribosome biogenesis and function

Sloan, Katherine E.; Warda, Ahmed S.; Sharma, Sunny; Entian, Karl‐Dieter; Lafontaine, Denis L. J.; Bohnsack, Markus T.

doi:10.1080/15476286.2016.1259781

Cited by 535 publications

(599 citation statements)

References 154 publications

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“…Approximately 2% of rRNA nucleotides are modified, corresponding to over 100 sites of modification in yeast and over 200 sites in humans. While the number of modifications is large, the diversity of modifications is small; most modifications are 2’- O -methylation of the sugar and Ψ (~50 each in yeast, and ~100 each in humans), although around 10 base modifications have also been identified in both humans and yeast (Sharma and Lafontaine, 2015; Sloan et al, 2016). …”

Section: Modifications In Abundant Noncoding Rnasmentioning

confidence: 99%

“…RNA-independent mechanisms exist in yeast, but are responsible for only two modifications. Pus7 installs Ψ at position 50 in 5S RNA and Spb1 installs the 2’-O-methylation at position 2922 in 25S RNA (Sloan et al, 2016). Stand-alone proteins install base modifications throughout the ribosome.…”

Section: Modifications In Abundant Noncoding Rnasmentioning

confidence: 99%

“…Instead, preventing the formation of two or more modifications within a cluster is typically required to observe a measurable phenotype. Cumulatively, rRNA modifications have been shown to affect cell growth and drug sensitivity as well as ribosome biogenesis, abundance, structure, and activity (Reviewed in Sloan et al, 2016). …”

Section: Modifications In Abundant Noncoding Rnasmentioning

confidence: 99%

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Dynamic RNA Modifications in Gene Expression Regulation

Roundtree

Evans

Pan

et al. 2017

Cell

2,484

2,401

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Over one hundred types of chemical modifications have been identified in cellular RNAs. While the 5’ cap modification and the poly(A) tail of eukaryotic messenger RNA play key roles in regulation, internal modifications are gaining attention for their roles in mRNA metabolism. The most abundant internal modification is N6-methyladenosine (m6A), and identification of proteins that install, recognize, and remove this and other marks have revealed roles for mRNA modification in nearly every aspect of the mRNA lifecycle, as well as in various cellular, developmental, and disease processes. Abundant noncoding RNAs such as transfer RNAs, ribosomal RNAs and spliceosomal RNAs are also heavily modified and depend on the modifications for their biogenesis and function. Our understanding of the biological contributions of these different chemical modifications is beginning to take shape, but it’s clear that in both coding and noncoding RNA, dynamic modifications represent a new layer of control of genetic information.

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Section: Modifications In Abundant Noncoding Rnasmentioning

confidence: 99%

Section: Modifications In Abundant Noncoding Rnasmentioning

confidence: 99%

Section: Modifications In Abundant Noncoding Rnasmentioning

confidence: 99%

See 1 more Smart Citation

Dynamic RNA Modifications in Gene Expression Regulation

Roundtree

Evans

Pan

et al. 2017

Cell

2,484

2,401

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“…This was particularly the case of the ribosome structure and tRNA population. However, evidence has progressively accumulated showing a broad variation of the composition of the ribosomes (Sauert et al 2015;Guimaraes and Zavolan 2016;Sloan et al 2016) and of the tRNA populations in response to environmental signals, during differentiation and diseases.…”

Section: The State Of the Trna Population In The Cellmentioning

confidence: 99%

Protein folding and tRNA biology

2017

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Polypeptides can fold into tertiary structures while they are synthesized by the ribosome. In addition to the amino acid sequence, protein folding is determined by several factors within the cell. Among others, the folding pathway of a nascent polypeptide can be affected by transient interactions with other proteins, ligands, or the ribosome, as well as by the translocation through membrane pores. Particularly, the translation machinery and the population of tRNA under different physiological or adaptive responses can dramatically affect protein folding. This review summarizes the scientific evidence describing the role of translation kinetics and tRNA populations on protein folding and addresses current efforts to better understand tRNA biology. It is organized into three main parts, which are focused on: (i) protein folding in the cellular context; (ii) tRNA biology and the complexity of the tRNA population; and (iii) available methods and technical challenges in the characterization of tRNA pools. In this manner, this work illustrates the ways by which functional properties of proteins may be modulated by cellular tRNA populations.

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“…In addition, we recovered a large number of snoRNA-rRNA interactions that are not predicted to direct methylation, but which would be expected to block methylation-guide interactions by other snoRNA species. Recent data point to the regulation of rRNA methylation levels in human cells (see for example ( Erales et al , 2017); reviewed by ( Sloan et al , 2017)) and at least one methylation and a pseudouridine site in the yeast rRNA are substoichiometric ( Buchhaupt et al , 2014; Taoka et al , 2016). Competitive interactions between snoRNAs offer a possible mechanism for regulating modification efficiencies.…”

Section: Discussionmentioning

confidence: 99%

Mapping targets for small nucleolar RNAs in yeast

Dudnakova¹,

Dunn-Davies²,

Peters³

et al. 2018

Wellcome Open Res

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Background: Recent analyses implicate changes in the expression of the box C/D class of small nucleolar RNAs (snoRNAs) in several human diseases. Methods: Here we report the identification of potential novel RNA targets for box C/D snoRNAs in budding yeast, using the approach of UV crosslinking and sequencing of hybrids (CLASH) with the snoRNP proteins Nop1, Nop56 and Nop58. We also developed a bioinformatics approach to filter snoRNA-target interactions for bona fide methylation guide interactions. Results: We recovered 241,420 hybrids, out of which 190,597 were classed as reproducible, high energy hybrids. As expected, the majority of snoRNA interactions were with the ribosomal RNAs (rRNAs). Following filtering, 117,047 reproducible hybrids included 51 of the 55 reported rRNA methylation sites. The majority of interactions at methylation sites were predicted to guide methylation. However, competing, potentially regulatory, binding was also identified. In marked contrast, following CLASH performed with the RNA helicase Mtr4 only 7% of snoRNA-rRNA interactions recovered were predicted to guide methylation. We propose that Mtr4 functions in dissociating inappropriate snoRNA-target interactions. Numerous snoRNA-snoRNA interactions were recovered, indicating potential cross regulation. The snoRNAs snR4 and snR45 were recently implicated in site-directed rRNA acetylation, and hybrids were identified adjacent to the acetylation sites. We also identified 1,368 reproducible snoRNA-mRNA interactions, representing 448 sites of interaction involving 39 snoRNAs and 382 mRNAs. Depletion of the snoRNAs U3, U14 or snR4 each altered the levels of numerous mRNAs. Targets identified by CLASH were over-represented among these species, but causality has yet to be established. Conclusions: Systematic mapping of snoRNA-target binding provides a catalogue of high-confidence binding sites and indicates numerous potential regulatory interactions.

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Tuning the ribosome: The influence of rRNA modification on eukaryotic ribosome biogenesis and function

Cited by 535 publications

References 154 publications

Dynamic RNA Modifications in Gene Expression Regulation

Dynamic RNA Modifications in Gene Expression Regulation

Protein folding and tRNA biology

Mapping targets for small nucleolar RNAs in yeast

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