A Functional Link between Nuclear RNA Decay and Transcriptional Control Mediated by the Polycomb Repressive Complex 2

Garland, William A.; Comet, Itys; Wu, Mengjun; Radzisheuskaya, Aliaksandra; Rib, Leonor; Vitting-Seerup, Kristoffer; Lloret-Llinares, Marta; Sandelin, Albin; Helin, Kristian; Jensen, Torben Heick

doi:10.1016/j.celrep.2019.10.011

Cited by 41 publications

(38 citation statements)

References 88 publications

(146 reference statements)

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“…This suggest that CPF recycling might be compromised in the exosome mutants and could explain why RNA hyperadenylation and 3'end extension is observed in the exosome mutants. In agreement with this idea, accumulation of nuclear RNAs upon exosome depletion was proposed to be a reason behind transcriptional de-repression of the Polycomb targets in mouse ESC (92). Figure 8C).…”

Section: Discussionsupporting

confidence: 68%

RNA-binding protein Mub1 and the nuclear RNA exosome act to fine-tune environmental stress response

Birot

Kilchert

Kuś

et al. 2020

Preprint

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ABSTRACTThe nuclear RNA exosome plays a key role in quality control and processing of multiple protein-coding and non-coding transcripts made by RNA polymerase II. A mechanistic understanding of exosome function remains a challenge given it has multiple roles in RNA regulation. Here we have analysed changes in the poly(A)+ RNA transcriptome and interactome provoked by mutations in three distinct subunits of the nuclear RNA exosome. We have identified multiple proteins whose occupancy on RNA is altered in the exosome mutants. We demonstrate that the Zinc-finger protein Mub1 regulates exosome dependent transcripts that encode stress-responsive proteins. Furthermore, we assess impact of the exosome inactivation upon RNA binding of the components of the mRNA processing machineries such as spliceosome and mRNA cleavage polyadenylation complex. We show that mutations in the exosome lead to accumulation of the components of U1 and U2 snRNPs on poly(A)+ RNA and depletion of the components of the activated spliceosome from RNA suggesting that the early stages of spliceosome assembly might provide a critical quality control step. Collectively, our data provide a global view of how RNA metabolism is affected in the exosome-deficient cells and reveal RNA-binding proteins that may act as novel exosome cofactors.

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Section: Discussionsupporting

confidence: 68%

RNA-binding protein Mub1 and the nuclear RNA exosome act to fine-tune environmental stress response

Birot

Kilchert

Kuś

et al. 2020

Preprint

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“…In agreement with this notion, it was proposed that the accumulation of the poly(A)-binding protein Nab2 on mRNAs upon nuclear export failure prevents its recycling to newly transcribed molecules (Tudek et al, 2018). In addition, the binding to chromatin of the human polycomb repressive complex 2 was found to be partially compromised, possibly because of its association with undigested ncRNAs in cells deleted for nuclear degradation factors (Garland et al, 2019).…”

Section: Discussionmentioning

confidence: 85%

Degradation of Non-coding RNAs Promotes Recycling of Termination Factors at Sites of Transcription

et al. 2020

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“…To determine whether the pattern of H3K4me1 distribution around the TSS was unique to germ cells, we applied the same data-processing protocol to published ChIP-seq data from mouse embryonic stem cells (mESCs) and human embryonic stem cells (hESCs) (Rada-Iglesias et al, 2011;Garland et al, 2019). The mixed unimodal/bimodal pattern of H3K4me1 density around the TSS was recapitulated in mESCs, and to a lesser degree in hESCs (Figure 2A).…”

Section: The Bimodal Distribution Is Characteristic Of H3k4me1 Acrossmentioning

confidence: 99%

H3K4me1 Distribution Predicts Transcription State and Poising at Promoters

Bae

Lesch

2020

Front. Cell Dev. Biol.

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Monomethylation on lysine 4 of histone H3 (H3K4me1) is commonly associated with distal enhancers, but H3K4me1 is also present at promoter regions proximal to transcription start sites. To assess a possible role for H3K4me1 in dictating gene regulatory states at promoters, we examined H3K4me1 peak density around promoters in human and mouse germ cells using an analytic strategy that allowed us to assess relationships between different epigenetic marks on a promoter-by-promoter basis. We found that H3K4me1 exhibits either a bimodal pattern at active promoters, where it flanks H3K4me3, or a unimodal pattern at poised promoters, where it coincides with both H3K4me3 and H3K27me3. This pattern is correlated with gene expression level, but is more strongly linked to a poised chromatin state, defined by the simultaneous presence of H3K4me3 and H3K27me3, than to transcriptional activity. The pattern is especially prominent in germ cells, but is also present in other cell types, including embryonic stem cells and differentiated somatic cells. We propose that H3K4me1 is a key feature of the poised epigenetic state, and suggest possible roles for this mark in epigenetic memory.

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A Functional Link between Nuclear RNA Decay and Transcriptional Control Mediated by the Polycomb Repressive Complex 2

Abstract: Highlights d Depletion of ZFC3H1 in mouse ESCs results in differentiation defects d PRC2 target genes are deregulated in Zfc3h1 À/À cells d Chromatin binding of PRC2 and H3K27me3 is reduced in Zfc3h1 À/À cells d Increased binding of RNA impairs PRC2 complex stability

Cited by 41 publications

References 88 publications

RNA-binding protein Mub1 and the nuclear RNA exosome act to fine-tune environmental stress response

RNA-binding protein Mub1 and the nuclear RNA exosome act to fine-tune environmental stress response

Degradation of Non-coding RNAs Promotes Recycling of Termination Factors at Sites of Transcription

H3K4me1 Distribution Predicts Transcription State and Poising at Promoters

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