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Lookup NU author(s): Dr Marina Danilenko, Caroline Dalgliesh, Dr Ingrid Ehrmann, Professor Alison Tyson-Capper, Dr Gavin ClowryORCiD, Professor David Elliott
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
SLM2 and Sam68 are splicing regulator paralogsthat usually overlap in function, yet only SLM2 andnot Sam68 controls the Neurexin2 AS4 exon importantfor brain function. Herein we find that SLM2and Sam68 similarly bind to Neurexin2 pre-mRNA,both within the mouse cortex and in vitro. Proteindomain-swap experiments identify a region includingthe STAR domain that differentiates SLM2and Sam68 activity in splicing target selection, andconfirm that this is not established via the variantamino acids involved in RNA contact. However, farfewer SLM2 and Sam68 RNA binding sites flank theNeurexin2 AS4 exon, compared with those flankingthe Neurexin1 and Neurexin3 AS4 exons under jointcontrol by both Sam68 and SLM2. Doubling bindingsite numbers switched paralog sensitivity, by placingthe Neurexin2 AS4 exon under joint splicing controlby both Sam68 and SLM2. Our data support amodel where the density of shared RNA binding sitesaround a target exon, rather than different paralog-specificprotein–RNA binding sites, controls functionaltarget specificity between SLM2 and Sam68on the Neurexin2 AS4 exon. Similar models mightexplain differential control by other splicing regulatorswithin families of paralogs with indistinguishable RNA binding sites.
Author(s): Danilenko M, Dalgliesh C, Pagliarini V, Naro C, Ehrmann I, Feracci M, Kheirollahi-Chadegani M, Tyson-Capper A, Clowry GJ, Fort P, Dominguez C, Sette C, Elliott DJ
Publication type: Article
Publication status: Published
Journal: Nucleic Acids Research
Year: 2017
Volume: 45
Issue: 7
Pages: 4120–4130
Print publication date: 20/04/2017
Online publication date: 19/12/2016
Acceptance date: 08/12/2016
Date deposited: 19/01/2017
ISSN (print): 0305-1048
ISSN (electronic): 1362-4962
Publisher: Oxford University Press
URL: http://dx.doi.org/10.1093/nar/gkw1277
DOI: 10.1093/nar/gkw1277
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