Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/83187
Title: An RRM–ZnF RNA recognition module targets RBM10 to exonic sequences to promote exon exclusion
Authors: Collins, Katherine M.
Kainov, Yaroslav A.
Christodolou, Evangelos
Ray, Debashish
Morris, Quaid
Hughes, Timothy
Taylor, Ian A.
Makeyev, Eugene V.
Ramos, Andres
Keywords: Introns
RNA Splicing
Exons
Issue Date: 2017
Source: Collins, 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.
Series/Report no.: Nucleic Acids Research
Abstract: RBM10 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.
URI: https://hdl.handle.net/10356/83187
http://hdl.handle.net/10220/42476
DOI: 10.1093/nar/gkx225
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.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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