The contribution of pseudouridine to stabilities and structure of RNAs

Kierzek, Elżbieta; Małgowska, Magdalena; Lisowiec, Jolanta; Turner, Douglas H.; Gdaniec, Zofia; Kierzek, Ryszard

doi:10.1093/nar/gkt1330

Cited by 213 publications

(224 citation statements)

References 45 publications

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“…3d). The extensive pseudouridylation, a modification resulting in stronger base pairing to all bases 22 , of this stretch of U2 snRNA could provide a mechanism by which this region is able to interact favorably with a diverse set of RNA sequences.…”

Section: Cc-by-nd 40 International License Peer-reviewed) Is the Autmentioning

confidence: 99%

A sequence-based, deep learning model accurately predicts RNA splicing branchpoints

Paggi

Bejerano

2017

Preprint

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Experimental detection of RNA splicing branchpoints, the nucleotide serving as the nucleophile in the first catalytic step of splicing, is difficult. To date, annotations exist for only 16-21% of 3' splice sites in the human genome and even these limited annotations have been shown to be plagued by noise. We develop a sequence-only, deep learning based branchpoint predictor, LaBranchoR, which we conclude predicts a correct branchpoint for over 90% of 3' splice sites genome-wide. Our predicted branchpoints show large agreement with trends observed in the raw data, but analysis of conservation signatures and overlap with pathogenic variants reveal that our predicted branchpoints are generally more reliable than the raw data itself. We use our predicted branchpoints to identify a sequence element upstream of branchpoints consistent with extended U2 snRNA base pairing, show an association between weak branchpoints and alternative splicing, and explore the effects of variants on branchpoints.

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Section: Cc-by-nd 40 International License Peer-reviewed) Is the Autmentioning

confidence: 99%

A sequence-based, deep learning model accurately predicts RNA splicing branchpoints

Paggi

Bejerano

2017

Preprint

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“…The role of Ψ remains poorly understood, although it is known that Ψ can affect the secondary structure and basepairing of RNA (Arnez and Steitz 1994;Davis 1995;Newby and Greenbaum 2002a;Hudson et al 2013;Kierzek et al 2014). In this way, Ψ's can stabilize tRNA folding and increase the fidelity of codon-anticodon interactions, stabilize certain stem-loop conformations of snRNAs, and enable ribosome assembly (Yarian et al 1999;Greenbaum 2001, 2002b;Nobles et al 2002;Cabello-Villegas and Nikonowicz 2005;Denmon et al 2011;Jack et al 2011;Penzo et al 2015).…”

Section: Introductionmentioning

confidence: 99%

mRNA pseudouridylation affects RNA metabolism in the parasite Toxoplasma gondii

Nakamoto

Lovejoy

Cygan

et al. 2017

RNA

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RNA contains over 100 modified nucleotides that are created post-transcriptionally, among which pseudouridine (Ψ) is one of the most abundant. Although it was one of the first modifications discovered, the biological role of this modification is still not fully understood. Recently, we reported that a pseudouridine synthase (TgPUS1) is necessary for differentiation of the singlecelled eukaryotic parasite Toxoplasma gondii from active to chronic infection. To better understand the biological role of pseudouridylation, we report here gel-based and deep-sequencing methods to identify TgPUS1-dependent Ψ's in Toxoplasma RNA, and the use of TgPUS1 mutants to examine the effect of this modification on mRNAs. In addition to identifying conserved sites of pseudouridylation in Toxoplasma rRNA, tRNA, and snRNA, we also report extensive pseudouridylation of Toxoplasma mRNAs, with the Ψ's being relatively depleted in the 3 ′ ′ ′ ′ ′ -UTR but enriched at position 1 of codons. We show that many Ψ's in tRNA and mRNA are dependent on the action of TgPUS1 and that TgPUS1-dependent mRNA Ψ's are enriched in developmentally regulated transcripts. RNA-seq data obtained from wild-type and TgPUS1-mutant parasites shows that genes containing a TgPUS1-dependent Ψ are relatively more abundant in mutant parasites, while pulse/chase labeling of RNA with 4-thiouracil shows that mRNAs containing TgPUS1-dependent Ψ have a modest but statistically significant increase in half-life in the mutant parasites. These data are some of the first evidence suggesting that mRNA Ψ's play an important biological role.

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“…This mark is also enriched at alternatively spliced introns and over long exons (Dominissini et al, 2012), suggesting a role in modulating splicing. Moreover, Y modifications in tRNAs stabilize secondary structures (Sundaram et al, 2000;Kierzek et al, 2014) and may do the same in mRNAs in which they are incorporated (Carlile et al, 2014;Schwartz et al, 2014b). Similarly, as tRNA modifications are known to direct cleavage of internally transcribed spacers, mRNA modifications could likewise direct transcript cleavage and subsequent turnover (Hughes and Ares, 1991;Kiss-László et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Chemical Modifications Mark Alternatively Spliced and Uncapped Messenger RNAs in Arabidopsis

et al. 2015

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Posttranscriptional chemical modification of RNA bases is a widespread and physiologically relevant regulator of RNA maturation, stability, and function. While modifications are best characterized in short, noncoding RNAs such as tRNAs, growing evidence indicates that mRNAs and long noncoding RNAs (lncRNAs) are likewise modified. Here, we apply our highthroughput annotation of modified ribonucleotides (HAMR) pipeline to identify and classify modifications that affect WatsonCrick base pairing at three different levels of the Arabidopsis thaliana transcriptome (polyadenylated, small, and degrading RNAs). We find this type of modifications primarily within uncapped, degrading mRNAs and lncRNAs, suggesting they are the cause or consequence of RNA turnover. Additionally, modifications within stable mRNAs tend to occur in alternatively spliced introns, suggesting they regulate splicing. Furthermore, these modifications target mRNAs with coherent functions, including stress responses. Thus, our comprehensive analysis across multiple RNA classes yields insights into the functions of covalent RNA modifications in plant transcriptomes.

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The contribution of pseudouridine to stabilities and structure of RNAs

Cited by 213 publications

References 45 publications

A sequence-based, deep learning model accurately predicts RNA splicing branchpoints

A sequence-based, deep learning model accurately predicts RNA splicing branchpoints

mRNA pseudouridylation affects RNA metabolism in the parasite Toxoplasma gondii

Chemical Modifications Mark Alternatively Spliced and Uncapped Messenger RNAs in Arabidopsis

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