Integrative transcriptomic analysis suggests new autoregulatory splicing events coupled with nonsense-mediated mRNA decay

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  • dc.contributor.author Pervouchine, Dmitri D.
  • dc.contributor.author Popov, Yaroslav
  • dc.contributor.author Berry, Andy
  • dc.contributor.author Borsari, Beatrice, 1992-
  • dc.contributor.author Frankish, Adam
  • dc.contributor.author Guigó Serra, Roderic
  • dc.date.accessioned 2019-09-25T07:56:42Z
  • dc.date.available 2019-09-25T07:56:42Z
  • dc.date.issued 2019
  • dc.description.abstract Nonsense-mediated decay (NMD) is a eukaryotic mRNA surveillance system that selectively degrades transcripts with premature termination codons (PTC). Many RNA-binding proteins (RBP) regulate their expression levels by a negative feedback loop, in which RBP binds its own pre-mRNA and causes alternative splicing to introduce a PTC. We present a bioinformatic analysis integrating three data sources, eCLIP assays for a large RBP panel, shRNA inactivation of NMD pathway, and shRNA-depletion of RBPs followed by RNA-seq, to identify novel such autoregulatory feedback loops. We show that RBPs frequently bind their own pre-mRNAs, their exons respond prominently to NMD pathway disruption, and that the responding exons are enriched with nearby eCLIP peaks. We confirm previously proposed models of autoregulation in SRSF7 and U2AF1 genes and present two novel models, in which (i) SFPQ binds its mRNA and promotes switching to an alternative distal 3'-UTR that is targeted by NMD, and (ii) RPS3 binding activates a poison 5'-splice site in its pre-mRNA that leads to a frame shift and degradation by NMD. We also suggest specific splicing events that could be implicated in autoregulatory feedback loops in RBM39, HNRNPM, and U2AF2 genes. The results are available through a UCSC Genome Browser track hub.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Pervouchine D, Popov Y, Berry A, Borsari B, Frankish A, Guigó R. Integrative transcriptomic analysis suggests new autoregulatory splicing events coupled with nonsense-mediated mRNA decay. Nucleic Acids Res. 2019;47(10):5293-306. DOI: 10.1093/nar/gkz193
  • dc.identifier.doi http://dx.doi.org/10.1093/nar/gkz193
  • dc.identifier.issn 0305-1048
  • dc.identifier.uri http://hdl.handle.net/10230/42323
  • dc.language.iso eng
  • dc.publisher Oxford University Press
  • dc.relation.ispartof Nucleic Acids Research. 2019;47(10):5293-306
  • dc.rights © 2019, Dmitri Pervouchine et al. Published by Oxford University Press. This is an Open Access article distributed under the terms of a Creative Commons Attribution License
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.title Integrative transcriptomic analysis suggests new autoregulatory splicing events coupled with nonsense-mediated mRNA decay
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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