Pumilio facilitates miRNA regulation of the E2F3 oncogene

Miles, Wayne; Tschöp, Katrin; Herr, Anabel; Ji, Jun-Yuan; Dyson, Nicholas J.

doi:10.1101/gad.182568.111

Cited by 143 publications

(170 citation statements)

References 55 publications

(86 reference statements)

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“…An intriguing possibility is that a PUF-Argonaute interaction could participate in combinatorial control of target mRNAs regulated by both PUFs and microRNAs. Interestingly, human and Drosophila PUMs were recently reported to collaborate with microRNA-mediated repression (Kedde et al 2010;Miles et al 2012). If true, we would anticipate that collaborative repression would be dependent on the major effector protein of microRNA-mediated repression, GW182 (Tritschler et al 2010).…”

Section: Pumilio Represses By Targeting Pabpmentioning

confidence: 94%

The RNA binding domain of Pumilio antagonizes poly-adenosine binding protein and accelerates deadenylation

Weidmann

Raynard

Blewett

et al. 2014

RNA

117

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PUF proteins are potent repressors that serve important roles in stem cell maintenance, neurological processes, and embryonic development. These functions are driven by PUF protein recognition of specific binding sites within the 3 ′ untranslated regions of target mRNAs. In this study, we investigated mechanisms of repression by the founding PUF, Drosophila Pumilio, and its human orthologs. Here, we evaluated a previously proposed model wherein the Pumilio RNA binding domain (RBD) binds Argonaute, which in turn blocks the translational activity of the eukaryotic elongation factor 1A. Surprisingly, we found that Argonautes are not necessary for repression elicited by Drosophila and human PUFs in vivo. A second model proposed that the RBD of Pumilio represses by recruiting deadenylases to shorten the mRNA's polyadenosine tail. Indeed, the RBD binds to the Pop2 deadenylase and accelerates deadenylation; however, this activity is not crucial for regulation. Rather, we determined that the poly(A) is necessary for repression by the RBD. Our results reveal that poly(A)-dependent repression by the RBD requires the poly(A) binding protein, pAbp. Furthermore, we show that repression by the human PUM2 RBD requires the pAbp ortholog, PABPC1. Pumilio associates with pAbp but does not disrupt binding of pAbp to the mRNA. Taken together, our data support a model wherein the Pumilio RBD antagonizes the ability of pAbp to promote translation. Thus, the conserved function of the PUF RBD is to bind specific mRNAs, antagonize pAbp function, and promote deadenylation.

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Section: Pumilio Represses By Targeting Pabpmentioning

confidence: 94%

The RNA binding domain of Pumilio antagonizes poly-adenosine binding protein and accelerates deadenylation

Weidmann

Raynard

Blewett

et al. 2014

RNA

117

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“…Indeed, PUM1 induces a structural change within the 3 ′ -UTR of the tumor suppressor cyclin-dependent kinase inhibitor 1B (CDKN1B/p27) transcript, thus permitting access to miR-221/222 with consequences for cell cycle progression (108) . Likewise, human PUM proteins cooperate with miRNAs for regulation of the transcription factor 3 (E2F3) oncogene (109) . Thus, in contrast to HuR and Dnd1 outlined above, PUM proteins and miRNA appear to interact synergistically to dampen gene expression.…”

Section: Combinatorial Control -Synergistic and Antagonistic Interactmentioning

confidence: 99%

RNA regulons and the RNA-protein interaction network

Imig¹,

Kanitz²,

Gerber

2012

BioMolecular Concepts

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The development of genome-wide analysis tools has prompted global investigation of the gene expression program, revealing highly coordinated control mechanisms that ensure proper spatiotemporal activity of a cell ' s macromolecular components. With respect to the regulation of RNA transcripts, the concept of RNA regulons, which -by analogy with DNA regulons in bacteria -refers to the coordinated control of functionally related RNA molecules, has emerged as a unifying theory that describes the logic of regulatory RNA-protein interactions in eukaryotes. Hundreds of RNA-binding proteins and small non-coding RNAs, such as microRNAs, bind to distinct elements in target RNAs, thereby exerting specifi c and concerted control over posttranscriptional events. In this review, we discuss recent reports committed to systematically explore the RNA-protein interaction network and outline some of the principles and recurring features of RNA regulons: the coordination of functionally related mRNAs through RNAbinding proteins or non-coding RNAs, the modular structure of its components, and the dynamic rewiring of RNA-protein interactions upon exposure to internal or external stimuli. We also summarize evidence for robust combinatorial control of mRNAs, which could determine the ultimate fate of each mRNA molecule in a cell. Finally, the compilation and integration of global protein-RNA interaction data has yielded fi rst insights into network structures and provided the hypothesis that RNA regulons may, in part, constitute noise ' buffers ' to handle stochasticity in cellular transcription.

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“…The cooperation is not limited to p27: there is evidence for a deeper involvement of both Pumilio proteins and miR-221/ 222 in the cell cycle misregulation leading to cancer progression. 4,38 In human, miR-221 and miR-222 have 90% identical targets with a total union of »1200 targets. The dataset of 19 RBPs contains PUM2 with 4078 targets.…”

Section: Case Study: the Interaction Of Pumilio And Mir-221/222 Is Rementioning

confidence: 99%

“…Moreover, Pumilio proteins have also been shown to be associated with the miRNA-based regulation of the E2F3 oncogenes. 38 There are also examples for competitive regulation where miRNA function is inhibited by RBPs. The RBP Dnd1 has been shown to inhibit the action of miR-21 on its target MSH2 and this regulation has also been implicated in in cancer devlopment.…”

Section: Introductionmentioning

confidence: 99%

SimiRa: A tool to identify coregulation between microRNAs and RNA-binding proteins

et al. 2015

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Abbreviations: miRNA, microRNA; RBP, RNA-binding protein microRNAs and microRNA-independent RNA-binding proteins are 2 classes of post-transcriptional regulators that have been shown to cooperate in gene-expression regulation. We compared the genome-wide target sets of microRNAs and RBPs identified by recent CLIP-Seq technologies, finding that RBPs have distinct target sets and favor gene interaction network hubs. To identify microRNAs and RBPs with a similar functional context, we developed simiRa, a tool that compares enriched functional categories such as pathways and GO terms. We applied simiRa to the known functional cooperation between Pumilio family proteins and miR-221/222 in the regulation of tumor supressor gene p27 and show that the cooperation is reflected by similar enriched categories but not by target genes. SimiRa also predicts possible cooperation of microRNAs and RBPs beyond direct interaction on the target mRNA for the nuclear RBP TAF15. To further facilitate research into cooperation of microRNAs and RBPs, we made simiRa available as a web tool that displays the functional neighborhood and similarity of microRNAs and RBPs: http://vsicb-simira.helmholtz-muenchen.de.

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Pumilio facilitates miRNA regulation of the E2F3 oncogene

Cited by 143 publications

References 55 publications

The RNA binding domain of Pumilio antagonizes poly-adenosine binding protein and accelerates deadenylation

The RNA binding domain of Pumilio antagonizes poly-adenosine binding protein and accelerates deadenylation

RNA regulons and the RNA-protein interaction network

SimiRa: A tool to identify coregulation between microRNAs and RNA-binding proteins

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