A role for the P-body component GW182 in microRNA function

Liu, Jidong; Rivas, Fabiola V.; Wohlschlegel, James A.; Yates, John R.; Parker, Roy; Hannon, Gregory J.

doi:10.1038/ncb1333

Cited by 601 publications

(582 citation statements)

References 30 publications

Supporting

Mentioning

550

Contrasting

Unclassified

Order By: Relevance

“…Finally, ERGmediated mRNA degradation relied on the presence of intact PBs within the cell, because preventing their formation with a short interfering RNA (siRNA) against the key PB component GW182 (ref. 28) significantly reduced degradation of the R-Luc-8MS2 mRNA by ERG ( Fig. 1g and Supplementary Fig.…”

Section: Erg Localizes To Pbs and Promotes Cytoplasmic Mrna Decaymentioning

confidence: 91%

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: Erg Localizes To Pbs and Promotes Cytoplasmic Mrna Decaymentioning

confidence: 91%

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

“…Plant miRNAs are also methylated on the ribose of the last nucleotide, a modification presumably involved in protecting miRNAs from 3′ end uridylation and degradation, whereas animal miRNAs do not appear to be modified Yu et al 2005). Mechanistically, most animal miRNAs are only partly complementary to their targets and mediate silencing primarily by translational repression, although localization to the processing bodies may also affect RNA stability (Humphreys et al 2005;Liu et al 2005b;Pillai et al 2005;Wienholds and Plasterk 2005;Zamore and Haley 2005). In contrast, most plant miRNAs have near-perfect complementarity to their targets and trigger predominantly mRNA cleavage (Carrington and Ambros 2003;Schwab et al 2005).…”

Section: Additional (Derived?) Functions Of the Rnai Machinerymentioning

confidence: 99%

On the origin and functions of RNA-mediated silencing: from protists to man

2006

View full text Add to dashboard Cite

Double-stranded RNA has been shown to induce gene silencing in diverse eukaryotes and by a variety of pathways. We have examined the taxonomic distribution and the phylogenetic relationship of key components of the RNA interference (RNAi) machinery in members of five eukaryotic supergroups. On the basis of the parsimony principle, our analyses suggest that a relatively complex RNAi machinery was already present in the last common ancestor of eukaryotes and consisted, at a minimum, of one Argonautelike polypeptide, one Piwi-like protein, one Dicer, and one RNAdependent RNA polymerase. As proposed before, the ancestral (but non-essential) role of these components may have been in defense responses against genomic parasites such as transposable elements and viruses. From a mechanistic perspective, the RNAi machinery in the eukaryotic ancestor may have been capable of both small-RNA-guided transcript degradation as well as transcriptional repression, most likely through histone modifications. Both roles appear to be widespread among living eukaryotes and this diversification of function could account for the evolutionary conservation of duplicated Argonaute-Piwi proteins. In contrast, additional RNAi-mediated pathways such as RNA-directed DNA methylation, programmed genome rearrangements, meiotic silencing by unpaired DNA, and miRNA-mediated gene regulation may have evolved independently in specific lineages.

show abstract

“…First, exogenously transfected siRNAs with no known endogenous mRNA targets localized to PBs (Jakymiw et al, 2005). Second, depletion by RNAi of PB components, such as GW182 protein, decapping enzymes (Dcp1a, Dcp2), RCK/p54 and the 5 0 -to-3 0 exonuclease Xrn1, impair both RNAi-and miRNA-mediated repression in flies worm and cultured human cells (Ding et al, 2005;Jakymiw et al, 2005;Rehwinkel et al, 2005;Liu et al, 2005a;Chu and Rana, 2006). Finally, Mov10, the human homologue of Armitage, a helicase required in flies for RISC assembly in the germ line, interacts with human Ago1 and Ago2 and is localized in the PBs.…”

Section: Mechanism(s) Of Mirna-mediated Gene Regulationmentioning

confidence: 99%

Principles and effects of microRNA-mediated post-transcriptional gene regulation

2006

View full text Add to dashboard Cite

MicroRNAs (miRNAs) are abundant regulatory RNAs involved in the regulation of many key biological processes. Recent advances in understanding the mechanism of RNA interference and miRNA-mediated mechanisms shed light on major principals of the formation of the regulatory complex and provide models to explain how these small regulatory RNA species interfere with gene expression and how they influence the translational status of the transcriptome.

show abstract

A role for the P-body component GW182 in microRNA function

Cited by 601 publications

References 30 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

On the origin and functions of RNA-mediated silencing: from protists to man

Principles and effects of microRNA-mediated post-transcriptional gene regulation

Contact Info

Product

Resources

About