RNA decay machines: Deadenylation by the Ccr4–Not and Pan2–Pan3 complexes

Wahle, Elmar; Winkler, G. Sebastiaan

doi:10.1016/j.bbagrm.2013.01.003

Cited by 216 publications

(267 citation statements)

References 132 publications

Supporting

Mentioning

251

Contrasting

Unclassified

Order By: Relevance

“…Therefore, a wide range of TFs and RBPs may actually collaborate in coupling transcriptional and post-transcriptional processes and machineries through the formation of highly versatile functional platforms. In terms of RNA degradation, targeting of the CCR4-NOT complex to specific mRNAs is known to involve interactions with sequence-specific RBPs 3 . On the basis of our study, we speculate that an additional level of specificity might be achieved through interactions with sequence-specific DNAbinding factors, such as ERG.…”

Section: Discussionmentioning

confidence: 99%

“…2c). Together, CNOT2 and CNOT3 form the NOT module, which is thought to mediate the recruitment of the deadenylase subunits of the CCR4-NOT complex to mRNAs targeted for degradation 3,33 . Indeed, ERG also coimmunoprecipitated with both deadenylase subunits CNOT6 (CCR4) and CNOT7 (CAF1), a result consistent with a function of ERG in mRNA decay ( Supplementary Fig.…”

Section: Erg Promotes Mrna Decay Through Recruitment Of Ccr4-notmentioning

confidence: 99%

See 1 more Smart Citation

The transcription factor ERG recruits CCR4–NOT to control mRNA decay and mitotic progression

Rambout

Detiffe

Bruyr

et al. 2016

Nat Struct Mol Biol

View full text Add to dashboard Cite

nature structural & molecular biology advance online publication a r t i c l e sAlthough undisputable evidence has clearly demonstrated that the nuclear steps of mRNA processing are mechanistically linked to transcription, a conceptual evolution in gene regulation has come with the realization that transcription might also be functionally connected to more remote processes occurring in the cytoplasm, such as mRNA decay 1,2 . Cytoplasmic mRNA decay is initiated by deadenylation, a rate-limiting event during which the poly(A) tail of the transcript is trimmed off by the CCR4-NOT complex, the main deadenylation machinery in eukaryotes 3 . The degradation of specific mRNAs, a key process in the regulation of eukaryotic gene expression, is achieved through the recruitment of the CCR4-NOT complex by sequence-specific RNA-binding proteins (RBPs) or by the microRNA machinery 3,4 . Poly(A)-shortened mRNAs, along with factors involved in the deadenylation, decapping and mRNA-degradation machineries, accumulate in microscopic mRNA-protein complex (mRNP) aggregates called processing bodies (PBs) 5 .The idea of coupling between mRNA synthesis and degradation has recently emerged. Genome-wide expression studies in yeast have shown that mRNA synthesis and decay are mechanistically and functionally coordinated, thus supporting the existence of common molecular effectors [6][7][8][9] . In particular, the CCR4-NOT deadenylation complex was first described as a transcriptional regulator and has been implicated in initiation and elongation by RNA polymerase II 10,11 . More surprisingly, it has also been shown that degradation of yeast mRNAs is determined by cis-acting sequence elements in promoters 12,13 . These findings have led to the concept of mRNA imprinting, in which sequence-specific DNA-binding factors might orchestrate mRNA synthesis and decay. This decay would occur via loading of factors regulating cytoplasmic mRNA degradation onto the transcribing mRNA 14 . However, the identity of these DNA-binding mRNA coordinators is still obscure, and it remains to be tested whether such coupling between transcription and decay also exists in higher eukaryotes. E26 (Ets) proteins, a family of 28 helix-loop-helix transcription factors (TFs) in metazoans, are characterized by a highly conserved DNA-binding ETS domain 15 . Through this domain, Ets factors bind specific gene promoters and act as key regulators in many biological processes including cellular proliferation, apoptosis, differentiation and survival 16 . ERG, FLI1 and the more structurally divergent FEV compose the Erg subfamily of Ets factors and have been identified as driving factors in prostate cancer, Ewing's tumors and leukemias 15,17 . Using ERG as a paradigm, we sought to investigate the possibility that eukaryotic transcription factors might be directly involved in cytoplasmic mRNA decay. We demonstrate that ERG triggers degradation of mRNAs connected to Aurora signaling by recruiting RBPs and the CCR4-NOT deadenylation complex and that this activity is important fo...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Erg Promotes Mrna Decay Through Recruitment Of Ccr4-notmentioning

confidence: 99%

The transcription factor ERG recruits CCR4–NOT to control mRNA decay and mitotic progression

Rambout

Detiffe

Bruyr

et al. 2016

Nat Struct Mol Biol

View full text Add to dashboard Cite

show abstract

“…In eukaryotes the deadenylation step is often rate limiting and involves the consecutive action of two different cytoplasmic deadenylase complexes (4)(5)(6). Initially, the poly(A) tail is trimmed by the PAN2-PAN3 complex, followed by a rapid degradation by the CCR4-NOT complex (4,5). Besides their general activity in the mRNA degradation pathway, both deadenylase complexes can get specifically recruited to mRNAs through RNA binding proteins.…”

mentioning

confidence: 99%

“…Alternatively, deadenylation can be followed by 3=-to-5= degradation through the exosome (1)(2)(3). In eukaryotes the deadenylation step is often rate limiting and involves the consecutive action of two different cytoplasmic deadenylase complexes (4)(5)(6). Initially, the poly(A) tail is trimmed by the PAN2-PAN3 complex, followed by a rapid degradation by the CCR4-NOT complex (4,5).…”

mentioning

confidence: 99%

General and MicroRNA-Mediated mRNA Degradation Occurs on Ribosome Complexes in Drosophila Cells

Antic

Wolfinger

Skucha

et al. 2015

Molecular and Cellular Biology

View full text Add to dashboard Cite

The translation and degradation of mRNAs are two key steps in gene expression that are highly regulated and targeted by many factors, including microRNAs (miRNAs). While it is well established that translation and mRNA degradation are tightly coupled, it is still not entirely clear where in the cell mRNA degradation takes place. In this study, we investigated the possibility of mRNA degradation on the ribosome in Drosophila cells. Using polysome profiles and ribosome affinity purification, we could demonstrate the copurification of various deadenylation and decapping factors with ribosome complexes. Also, AGO1 and GW182, two key factors in the miRNA-mediated mRNA degradation pathway, were associated with ribosome complexes. Their copurification was dependent on intact mRNAs, suggesting the association of these factors with the mRNA rather than the ribosome itself. Furthermore, we isolated decapped mRNA degradation intermediates from ribosome complexes and performed high-throughput sequencing analysis. Interestingly, 93% of the decapped mRNA fragments (approximately 12,000) could be detected at the same relative abundance on ribosome complexes and in cell lysates. In summary, our findings strongly indicate the association of the majority of bulk mRNAs as well as mRNAs targeted by miRNAs with the ribosome during their degradation.

show abstract

“…63 Translational repression of miRNA-targeted mRNAs is usually followed in short succession by their degradation, which is initiated by the Ago2-and GW182-dependent recruitment of deadenylase complexes. 9,11,12 There are two such complexes in eukaryotes: the multi-protein, 1 MDa Ccr4-NOT, and the two-subunit Pan2-Pan3 complex (for extensive reviews of their structure and function, see Wahle and Winkler 97 and Collart and Panasenko 98 ). The Ccr4-NOT complex comprises two catalytic subunits-Ccr4 (CNOT6 and CNOT6L in mammals) and Caf1 (CNOT7, CNOT8 and Caf1z in mammals).…”

mentioning

confidence: 99%

The complexity of miRNA-mediated repression

2014

View full text Add to dashboard Cite

Since their discovery 20 years ago, miRNAs have attracted much attention from all areas of biology. These short (B22 nt) non-coding RNA molecules are highly conserved in evolution and are present in nearly all eukaryotes. They have critical roles in virtually every cellular process, particularly determination of cell fate in development and regulation of the cell cycle. Although it has long been known that miRNAs bind to mRNAs to trigger translational repression and degradation, there had been much debate regarding their precise mode of action. It is now believed that translational control is the primary event, only later followed by mRNA destabilisation. This review will discuss the most recent advances in our understanding of the molecular underpinnings of miRNA-mediated repression. Moreover, we highlight the multitude of regulatory mechanisms that modulate miRNA function.

show abstract

RNA decay machines: Deadenylation by the Ccr4–Not and Pan2–Pan3 complexes

Cited by 216 publications

References 132 publications

The transcription factor ERG recruits CCR4–NOT to control mRNA decay and mitotic progression

The transcription factor ERG recruits CCR4–NOT to control mRNA decay and mitotic progression

General and MicroRNA-Mediated mRNA Degradation Occurs on Ribosome Complexes in Drosophila Cells

The complexity of miRNA-mediated repression

Contact Info

Product

Resources

About