Identification of the RNA recognition element of the RBPMS family of RNA-binding proteins and their transcriptome-wide mRNA targets

Farazi, Thalia A.; Leonhardt, Carl S.; Mukherjee, Neelanjan; Mihailović, Aleksandra; Li, Song; Max, Klaas E.A.; Meyer, Cindy; Yamaji, Masashi; Čekan, Pavol; Jacobs, Nicholas C; Gerstberger, Stefanie; Bognanni, Claudia; Larsson, Erik; Ohler, Uwe; Tuschl, Thomas

doi:10.1261/rna.045005.114

Cited by 57 publications

(85 citation statements)

References 53 publications

(61 reference statements)

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“…With this approach, we identified 196 mRNAs (corresponding to 186 individual genes) whose stability was most significantly increased in the absence of ERG (Fig. 4a, green 36 , we found that these ERG degradation targets were strongly enriched in RBPMSassociated mRNAs, thus supporting a functional role for RBPMS in ERG-mediated decay (Fig. 4b).…”

Section: Erg Rbpms and Cnot2 Promote Degradation Of Mitotic Mrnasmentioning

confidence: 75%

“…Strikingly, the set of ERG interactors identified in our Y2H screen also included RNA-binding Fox-1 (RBFOX1 or A2BP1) and RNA-binding protein with multiple splicing (RBPMS or Hermes), two RBPs with canonical RNA-recognition motifs 34,35 (Supplementary Table 1). Whereas RBFOX proteins are wellcharacterized splicing factors, the role of RBPMS in mRNA processing remains unclear 36,37 . From these findings, we hypothesized that ERG might be recruited to specific mRNAs through its interaction with RBPs including RBPMS.…”

Section: Erg Is Recruited To Mrna Via Its Interaction With Rbpsmentioning

confidence: 99%

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

Rambout

Detiffe

Bruyr

et al. 2016

Nat Struct Mol Biol

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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...

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Section: Erg Rbpms and Cnot2 Promote Degradation Of Mitotic Mrnasmentioning

confidence: 75%

Section: Erg Is Recruited To Mrna Via Its Interaction With Rbpsmentioning

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

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“…Other resources have started to collect RNA interactions Hao et al 2016;Junge et al 2017;Yi et al 2017). However, new interactions are continuously published for yeast and mammalian mRNAs (Baltz et al 2012;Baejen et al 2014;Farazi et al 2014;Gerstberger et al 2014;Castello et al 2016b) and for less characterized classes of ncRNAs such as SUT, CUT, and XUT (Tuck and Tollervey 2013). We believe that it is extremely timely to begin to collate RNA interaction data from the literature and high-throughput experimental screens.…”

Section: Discussionmentioning

confidence: 99%

The yeast noncoding RNA interaction network

Panni

Prakash

Bateman

et al. 2017

RNA

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This article describes the creation of the first expert manually curated noncoding RNA interaction networks for S. cerevisiae. The RNA-RNA and RNA-protein interaction networks have been carefully extracted from the experimental literature and made available through the IntAct database (www.ebi.ac.uk/intact). We provide an initial network analysis and compare their properties to the much larger protein-protein interaction network. We find that the proteins that bind to ncRNAs in the network contain only a small proportion of classical RNA binding domains. We also see an enrichment of WD40 domains suggesting their direct involvement in ncRNA interactions. We discuss the challenges in collecting noncoding RNA interaction data and the opportunities for worldwide collaboration to fill the unmet need for this data.

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“…Our results indicate that Hermes is a repressor of nrp1 mRNA translation, either directly or indirectly, which controls Nrp1 expression temporally in RGC growth cones. Interestingly, the mammalian ortholog of Hermes, RBPMS2, has also been shown to bind to nrp1 mRNA (Farazi et al, 2014). …”

Section: Discussionmentioning

confidence: 99%

Hermes Regulates Axon Sorting in the Optic Tract by Post-Trancriptional Regulation of Neuropilin 1

et al. 2016

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The establishment of precise topographic maps during neural development is facilitated by the presorting of axons in the pathway before they reach their targets. In the vertebrate visual system, such topography is seen clearly in the optic tract (OT) and in the optic radiations. However, the molecular mechanisms involved in pretarget axon sorting are poorly understood. Here, we show in zebrafish that the RNA-binding protein Hermes, which is expressed exclusively in retinal ganglion cells (RGCs), is involved in this process. Using a RiboTag approach, we show that Hermes acts as a negative translational regulator of specific mRNAs in RGCs. One of these targets is the guidance cue receptor Neuropilin 1 (Nrp1), which is sensitive to the repellent cue Semaphorin 3A (Sema3A). Hermes knock-down leads to topographic missorting in the OT through the upregulation of Nrp1. Restoring Nrp1 to appropriate levels in Hermes-depleted embryos rescues this effect and corrects the axon-sorting defect in the OT. Our data indicate that axon sorting relies on Hermes-regulated translation of Nrp1.SIGNIFICANCE STATEMENT An important mechanism governing the formation of the mature neural map is pretarget axon sorting within the sensory tract; however, the molecular mechanisms involved in this process remain largely unknown. The work presented here reveals a novel function for the RNA-binding protein Hermes in regulating the topographic sorting of retinal ganglion cell (RGC) axons in the optic tract and tectum. We find that Hermes negatively controls the translation of the guidance cue receptor Neuropilin-1 in RGCs, with Hermes knock-down resulting in aberrant growth cone cue sensitivity and axonal topographic misprojections. We characterize a novel RNA-based mechanism by which axons restrict their translatome developmentally to achieve proper targeting.

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Identification of the RNA recognition element of the RBPMS family of RNA-binding proteins and their transcriptome-wide mRNA targets

Cited by 57 publications

References 53 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

The yeast noncoding RNA interaction network

Hermes Regulates Axon Sorting in the Optic Tract by Post-Trancriptional Regulation of Neuropilin 1

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