Functional characterization of Upf1 targets in<i>Schizosaccharomyces pombe</i>

Matia-González, Ana M.; Hasan, Ayesha; Moe, Gøril H.; Mata, Juan; Gabriel, M.

doi:10.4161/rna.24569

Cited by 11 publications

(19 citation statements)

References 38 publications

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“…Surprisingly, a substantial number (∼50) of RNAs bound by Zfs1 and Scw1 overlapped (Table S9). However, these RNAs were not enriched in those associated with Red1 or other any S. pombe proteins that we had previously investigated by RIp-chip [12], [62]–[66]. Given the specificity of this overlap, it seems unlikely to represent a technical artefact, and could be explained if the two proteins are located to the same subcellular structure that co-purifies with them.…”

Section: Resultsmentioning

confidence: 85%

Systematic Analysis of the Role of RNA-Binding Proteins in the Regulation of RNA Stability

et al. 2014

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mRNA half-lives are transcript-specific and vary over a range of more than 100-fold in eukaryotic cells. mRNA stabilities can be regulated by sequence-specific RNA-binding proteins (RBPs), which bind to regulatory sequence elements and modulate the interaction of the mRNA with the cellular RNA degradation machinery. However, it is unclear if this kind of regulation is sufficient to explain the large range of mRNA stabilities. To address this question, we examined the transcriptome of 74 Schizosaccharomyces pombe strains carrying deletions in non-essential genes encoding predicted RBPs (86% of all such genes). We identified 25 strains that displayed changes in the levels of between 4 and 104 mRNAs. The putative targets of these RBPs formed biologically coherent groups, defining regulons involved in cell separation, ribosome biogenesis, meiotic progression, stress responses and mitochondrial function. Moreover, mRNAs in these groups were enriched in specific sequence motifs in their coding sequences and untranslated regions, suggesting that they are coregulated at the posttranscriptional level. We performed genome-wide RNA stability measurements for several RBP mutants, and confirmed that the altered mRNA levels were caused by changes in their stabilities. Although RBPs regulate the decay rates of multiple regulons, only 16% of all S. pombe mRNAs were affected in any of the 74 deletion strains. This suggests that other players or mechanisms are required to generate the observed range of RNA half-lives of a eukaryotic transcriptome.

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Section: Resultsmentioning

confidence: 85%

Systematic Analysis of the Role of RNA-Binding Proteins in the Regulation of RNA Stability

et al. 2014

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“…RNA surveillance pathways is also linked to gene regulation during stress. For instance, a connection between the Nonsense-mediated mRNA decay surveillance pathway (NMD) and mRNA levels during oxidative stress has been observed in fission yeast 55 , 56 . Moreover, NMD participates in the regulation of ribosomal protein expression during the osmotic stress response in budding yeast 57 .…”

Section: Resultsmentioning

confidence: 99%

Contributions of transcription and mRNA decay to gene expression dynamics of fission yeast in response to oxidative stress

et al. 2014

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The cooperation of transcriptional and post-transcriptional levels of control to shape gene regulation is only partially understood. Here we show that a combination of two simple and non-invasive genomic techniques, coupled with kinetic mathematical modeling, affords insight into the intricate dynamics of RNA regulation in response to oxidative stress in the fission yeast Schizosaccharomyces pombe. This study reveals a dominant role of transcriptional regulation in response to stress, but also points to the first minutes after stress induction as a critical time when the coordinated control of mRNA turnover can support the control of transcription for rapid gene regulation. In addition, we uncover specialized gene expression strategies associated with distinct functional gene groups, such as simultaneous transcriptional repression and mRNA destabilization for genes encoding ribosomal proteins, delayed mRNA destabilization with varying contribution of transcription for ribosome biogenesis genes, dominant roles of mRNA stabilization for genes functioning in protein degradation, and adjustment of both transcription and mRNA turnover during the adaptation to stress. We also show that genes regulated independently of the bZIP transcription factor Atf1p are predominantly controlled by mRNA turnover, and identify putative cis-regulatory sequences that are associated with different gene expression strategies during the stress response. This study highlights the intricate and multi-faceted interplay between transcription and RNA turnover during the dynamic regulatory response to stress.

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“…; Matia‐González et al . ). Another attractive possibility is that NMD factors and SWI/SNF components control noncoding RNAs from the centromere core domain.…”

Section: Discussionmentioning

confidence: 97%

Schizosaccharomyces pombe centromere protein Mis19 links Mis16 and Mis18 to recruit CENP‐A through interacting with NMD factors and the SWI/SNF complex

et al. 2014

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Japan CENP-A is a centromere-specific variant of histone H3 that is required for accurate chromosome segregation. The fission yeast Schizosaccharomyces pombe and mammalian Mis16 and Mis18 form a complex essential for CENP-A recruitment to centromeres. It is unclear, however, how the Mis16-Mis18 complex achieves this function. Here, we identified, by mass spectrometry, novel fission yeast centromere proteins Mis19 and Mis20 that directly interact with Mis16 and Mis18. Like Mis18, Mis19 and Mis20 are localized at the centromeres during interphase, but not in mitosis. Inactivation of Mis19 in a newly isolated temperature-sensitive mutant resulted in CENP-A delocalization and massive chromosome missegregation, whereas Mis20 was dispensable for proper chromosome segregation. Mis19 might be a bridge component for Mis16 and Mis18. We isolated extragenic suppressor mutants for temperature-sensitive mis18 and mis19 mutants and used whole-genome sequencing to determine the mutated sites. We identified two groups of loss-of-function suppressor mutations in non-sense-mediated mRNA decay factors (upf2 and ebs1), and in SWI/SNF chromatin-remodeling components (snf5, snf22 and sol1). Our results suggest that the Mis16-Mis18-Mis19-Mis20 CENP-A-recruiting complex, which is functional in the G1-S phase, may be counteracted by the SWI/SNF chromatinremodeling complex and non-sense-mediated mRNA decay, which may prevent CENP-A deposition at the centromere.

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Functional characterization of Upf1 targets inSchizosaccharomyces pombe

Cited by 11 publications

References 38 publications

Systematic Analysis of the Role of RNA-Binding Proteins in the Regulation of RNA Stability

Systematic Analysis of the Role of RNA-Binding Proteins in the Regulation of RNA Stability

Contributions of transcription and mRNA decay to gene expression dynamics of fission yeast in response to oxidative stress

Schizosaccharomyces pombe centromere protein Mis19 links Mis16 and Mis18 to recruit CENP‐A through interacting with NMD factors and the SWI/SNF complex

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