RNA Exosomes and Their Cofactors

Kilchert, Cornelia

doi:10.1007/978-1-4939-9822-7_11

Cited by 9 publications

(5 citation statements)

References 146 publications

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“…Many processing defects that induce the retention of specific transcripts on chromatin are linked to the degradation of the retained transcript by the nuclear exosome (Assenholt et al, 2008; Hilleren et al, 2001; Kilchert et al, 2016). Notably, we find that Dbp2 both co-purifies and co-localizes with MTREC, the nuclear exosome targeting complex related to human PAXT composed of the Mtr4-like helicase Mtl1, the zinc-finger protein Red1, and various associated factors including the nuclear poly(A)-binding protein Pab2 (Egan et al, 2014; Kilchert, 2020; N. N. Lee et al, 2013; Meola et al, 2016; Silla et al, 2020; Zhou et al, 2015).…”

Section: Discussionmentioning

confidence: 87%

DEAD-box ATPase Dbp2 mediates mRNA release after 3'-end formation

Aydin,

Boehme,

Keil

et al. 2024

Preprint

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mRNA biogenesis in the eukaryotic nucleus is a highly complex process. The numerous RNA processing steps are tightly coordinated to ensure that only fully processed transcripts are released from chromatin for export from the nucleus. Here, we present the hypothesis that fission yeast Dbp2, a ribonucleoprotein complex (RNP) remodelling ATPase of the DEAD-box family, is the key enzyme in an RNP assembly checkpoint at the 3'-end of genes. We show that Dbp2 interacts with the cleavage and polyadenylation complex (CPAC) and localizes to cleavage bodies, which are enriched for 3'-end processing factors and proteins involved in nuclear RNA surveillance. Upon loss of Dbp2, 3'-processed, polyadenylated RNAs accumulate on chromatin and in cleavage bodies, and CPAC components are depleted from the soluble pool. Under these conditions, cells display an increased likelihood to skip polyadenylation sites and a delayed transcription termination, suggesting that levels of free CPAC components are insufficient to maintain normal levels of 3'-end processing. Our data support a model in which Dbp2 is the active component of an mRNP remodelling checkpoint that licenses RNA export and is coupled to CPAC release.

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Section: Discussionmentioning

confidence: 87%

DEAD-box ATPase Dbp2 mediates mRNA release after 3'-end formation

Aydin,

Boehme,

Keil

et al. 2024

Preprint

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“…The 3′–5′ exonucleolytic decay is mediated by the large, multi‐protein RNA exosome complex (reviewed in Łabno et al, 2016). The RNA exosome has widespread roles in the processing and degradation of both nuclear and cytoplasmic RNAs, with many target‐specific cofactors (reviewed in Kilchert, 2020). For human cytoplasmic mRNA degradation, the core RNA exosome with the DIS3L catalytic subunit is recruited to the 3′‐end of deadenylated or cleaved transcripts (Kilchert, 2020; Łabno et al, 2016).…”

Section: Mrna Degradation and The Integrated Stress Responsementioning

confidence: 99%

“…The RNA exosome has widespread roles in the processing and degradation of both nuclear and cytoplasmic RNAs, with many target-specific cofactors (reviewed in Kilchert, 2020). For human cytoplasmic mRNA degradation, the core RNA exosome with the DIS3L catalytic subunit is recruited to the 3 0 -end of deadenylated or cleaved transcripts (Kilchert, 2020;Łabno et al, 2016). For degradation of defective mRNAs first cleaved by endonucleases, the SKI complex is important for RNA exosome recruitment (van Hoof et al, 2002).…”

Section: Mechanisms Of Mrna Degradationmentioning

confidence: 99%

A (dis)integrated stress response: Genetic diseases of eIF2α regulators

2021

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The integrated stress response (ISR) is a conserved mechanism by which eukaryotic cells remodel gene expression to adapt to intrinsic and extrinsic stressors rapidly and reversibly. The ISR is initiated when stress-activated protein kinases phosphorylate the major translation initiation factor eukaryotic translation initiation factor 2ɑ (eIF2ɑ), which globally suppresses translation initiation activity and permits the selective translation of stress-induced genes including important transcription factors such as activating transcription factor 4 (ATF4). Translationally repressed messenger RNAs (mRNAs) and noncoding RNAs assemble into cytoplasmic RNA-protein granules and polyadenylated RNAs are concomitantly stabilized. Thus, regulated changes in mRNA translation, stability, and localization to RNA-protein granules contribute to the reprogramming of gene expression that defines the ISR. We discuss fundamental mechanisms of RNA regulation during the ISR and provide an overview of a growing class of genetic disorders associated with mutant alleles of key translation factors in the ISR pathway.

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“…The RNA exosome regulates levels of various cellular RNAs (Kilchert et al 2016;Morton et al 2018). On its own, the exosome is an unspecific RNA-degrading enzyme with low intrinsic nuclease activity; it requires cofactors to ensure selective and efficient degradation of its substrates (Schmid and Jensen 2019;Kilchert 2020). Conserved Ski2-like RNA helicases are thought to constitute targeting platforms for various substrate-selecting cofactors.…”

Section: Rna Exosome Regulatory Factors Are Rna-binding Proteinsmentioning

confidence: 99%