Backmasking in the yeast genome: encoding overlapping information for protein-coding and RNA degradation

Cakiroglu, Sera Aylin; Zaugg, Judith B.; Luscombe, Nicholas M.

doi:10.1093/nar/gkw683

Cited by 15 publications

(12 citation statements)

References 38 publications

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“…Accordingly, NRD1 mRNA levels are significantly reduced in rtr1Δ (Fig 2) and a corresponding 10% reduction in Nrd1 protein levels was also observed (S2 Fig). Secondly, Nrd1/Nab3 binding sites have been shown to PLOS GENETICS occur at a low frequency in protein coding mRNA transcripts yet occur at high frequency in ASTs [99]. The depletion of high affinity Nrd1/Nab3 binding sites from most protein coding genes likely limits premature termination of mRNAs.…”

Section: Discussionmentioning

confidence: 99%

RNA Polymerase II CTD phosphatase Rtr1 fine-tunes transcription termination

et al. 2020

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RNA Polymerase II (RNAPII) transcription termination is regulated by the phosphorylation status of the C-terminal domain (CTD). The phosphatase Rtr1 has been shown to regulate serine 5 phosphorylation on the CTD; however, its role in the regulation of RNAPII termination has not been explored. As a consequence of RTR1 deletion, interactions within the termination machinery and between the termination machinery and RNAPII were altered as quantified by Disruption-Compensation (DisCo) network analysis. Of note, interactions between RNAPII and the cleavage factor IA (CF1A) subunit Pcf11 were reduced in rtr1Δ, whereas interactions with the CTD and RNA-binding termination factor Nrd1 were increased. Globally, rtr1Δ leads to decreases in numerous noncoding RNAs that are linked to the Nrd1, Nab3 and Sen1 (NNS)-dependent RNAPII termination pathway. Genome-wide analysis of RNAPII and Nrd1 occupancy suggests that loss of RTR1 leads to increased termination at noncoding genes. Additionally, premature RNAPII termination increases globally at protein-coding genes with a decrease in RNAPII occupancy occurring just after the peak of Nrd1 recruitment during early elongation. The effects of rtr1Δ on RNA expression levels were lost following deletion of the exosome subunit Rrp6, which works with the NNS complex to rapidly degrade a number of noncoding RNAs following termination. Overall, these data suggest that Rtr1 restricts the NNS-dependent termination pathway in WT cells to prevent premature termination of mRNAs and ncRNAs. Rtr1 facilitates low-level elongation of noncoding transcripts that impact RNAPII interference thereby shaping the transcriptome.

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Section: Discussionmentioning

confidence: 99%

RNA Polymerase II CTD phosphatase Rtr1 fine-tunes transcription termination

et al. 2020

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“…This specificity can be attributed to a generally higher density of NNS complex binding sites within these RNAs as compared to e.g. mRNA 5′ end regions ( 21 ), as well as an interaction of Nrd1p with the Ser5-phosphorylated (Ser5p) C-terminal domain (CTD) of RNAPII, which is prevalent early during the transcription process ( 20 ).…”

Section: Introductionmentioning

confidence: 99%

ARS2 is a general suppressor of pervasive transcription

Iasillo

Schmid

Yahia

et al. 2017

Nucleic Acids Research

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Termination of transcription is important for establishing gene punctuation marks. It is also critical for suppressing many of the pervasive transcription events occurring throughout eukaryotic genomes and coupling their RNA products to efficient decay. In human cells, the ARS2 protein has been implicated in such function as its depletion causes transcriptional read-through of selected gene terminators and because it physically interacts with the ribonucleolytic nuclear RNA exosome. Here, we study the role of ARS2 on transcription and RNA metabolism genome wide. We show that ARS2 depletion negatively impacts levels of promoter-proximal RNA polymerase II at protein-coding (pc) genes. Moreover, our results reveal a general role of ARS2 in transcription termination-coupled RNA turnover at short transcription units like snRNA-, replication-dependent histone-, promoter upstream transcript- and enhancer RNA-loci. Depletion of the ARS2 interaction partner ZC3H18 mimics the ARS2 depletion, although to a milder extent, whereas depletion of the exosome core subunit RRP40 only impacts RNA abundance post-transcriptionally. Interestingly, ARS2 is also involved in transcription termination events within first introns of pc genes. Our work therefore establishes ARS2 as a general suppressor of pervasive transcription with the potential to regulate pc gene expression.

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“…Exonic splice enhancers (ESEs) are the class of regulatory signals whose impact on CDS evolution has been most thoroughly demonstrated [although other kinds of non-coding information have also been studied (e.g. Agoglia and Fraser 2016 ; Birnbaum et al 2014 ; Cakiroglu et al 2016 ; Hurst 2006 ; Itzkovitz et al 2010 ; Lin et al 2011 ; Liu et al 2015 ; Shabalina et al 2013 ; Stergachis et al 2013 ; Warnecke et al 2008a ; Xing and He 2015 )]. ESEs are short RNA motifs that promote the splicing of the exon in which they are contained.…”

Section: Introductionmentioning

confidence: 99%

Estimating the prevalence of functional exonic splice regulatory information

Savisaar

Hurst

2017

Hum Genet

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In addition to coding information, human exons contain sequences necessary for correct splicing. These elements are known to be under purifying selection and their disruption can cause disease. However, the density of functional exonic splicing information remains profoundly uncertain. Several groups have experimentally investigated how mutations at different exonic positions affect splicing. They have found splice information to be distributed widely in exons, with one estimate putting the proportion of splicing-relevant nucleotides at >90%. These results suggest that splicing could place a major pressure on exon evolution. However, analyses of sequence conservation have concluded that the need to preserve splice regulatory signals only slightly constrains exon evolution, with a resulting decrease in the average human rate of synonymous evolution of only 1–4%. Why do these two lines of research come to such different conclusions? Among other reasons, we suggest that the methods are measuring different things: one assays the density of sites that affect splicing, the other the density of sites whose effects on splicing are visible to selection. In addition, the experimental methods typically consider short exons, thereby enriching for nucleotides close to the splice junction, such sites being enriched for splice-control elements. By contrast, in part owing to correction for nucleotide composition biases and to the assumption that constraint only operates on exon ends, the conservation-based methods can be overly conservative.Electronic supplementary materialThe online version of this article (doi:10.1007/s00439-017-1798-3) contains supplementary material, which is available to authorized users.

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Backmasking in the yeast genome: encoding overlapping information for protein-coding and RNA degradation

Cited by 15 publications

References 38 publications

RNA Polymerase II CTD phosphatase Rtr1 fine-tunes transcription termination

RNA Polymerase II CTD phosphatase Rtr1 fine-tunes transcription termination

ARS2 is a general suppressor of pervasive transcription

Estimating the prevalence of functional exonic splice regulatory information

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