dc.contributor.authorCollins, Katherine M.
dc.contributor.authorKainov, Yaroslav A.
dc.contributor.authorChristodolou, Evangelos
dc.contributor.authorRay, Debashish
dc.contributor.authorMorris, Quaid
dc.contributor.authorHughes, Timothy
dc.contributor.authorTaylor, Ian A.
dc.contributor.authorMakeyev, Eugene V.
dc.contributor.authorRamos, Andres
dc.date.accessioned2017-05-24T03:12:29Z
dc.date.available2017-05-24T03:12:29Z
dc.date.issued2017
dc.identifier.citationCollins, K. M., Kainov, Y. A., Christodolou, E., Ray, D., Morris, Q., Hughes, T., Taylor, I. A., Makeyev, E. V.,& Ramos, A. (2017). An RRM–ZnF RNA recognition module targets RBM10 to exonic sequences to promote exon exclusion. Nucleic Acids Research.en_US
dc.identifier.urihttp://hdl.handle.net/10220/42476
dc.description.abstractRBM10 is an RNA-binding protein that plays an essential role in development and is frequently mutated in the context of human disease. RBM10 recognizes a diverse set of RNA motifs in introns and exons and regulates alternative splicing. However, the molecular mechanisms underlying this seemingly relaxed sequence specificity are not understood and functional studies have focused on 3΄ intronic sites only. Here, we dissect the RNA code recognized by RBM10 and relate it to the splicing regulatory function of this protein. We show that a two-domain RRM1–ZnF unit recognizes a GGA-centered motif enriched in RBM10 exonic sites with high affinity and specificity and test that the interaction with these exonic sequences promotes exon skipping. Importantly, a second RRM domain (RRM2) of RBM10 recognizes a C-rich sequence, which explains its known interaction with the intronic 3΄ site of NUMB exon 9 contributing to regulation of the Notch pathway in cancer. Together, these findings explain RBM10's broad RNA specificity and suggest that RBM10 functions as a splicing regulator using two RNA-binding units with different specificities to promote exon skipping.en_US
dc.description.sponsorshipNMRC (Natl Medical Research Council, S’pore)en_US
dc.format.extent14 p.en_US
dc.language.isoenen_US
dc.relation.ispartofseriesNucleic Acids Researchen_US
dc.rights© The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ttp://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.en_US
dc.subjectExonsen_US
dc.subjectIntronsen_US
dc.subjectRNA Splicingen_US
dc.titleAn RRM–ZnF RNA recognition module targets RBM10 to exonic sequences to promote exon exclusionen_US
dc.typeJournal Article
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.identifier.doihttp://dx.doi.org/10.1093/nar/gkx225
dc.description.versionPublished versionen_US


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