Context-dependent regulatory mechanism of the splicing factor hnRNP L.

Molecular Cell
Laura B Motta-MenaKristen W Lynch

Abstract

Splicing regulatory proteins often have distinct activities when bound to exons versus introns. However, less clear is whether variables aside from location can influence activity. HnRNP L binds to a motif present in both CD45 variable exons 4 and 5 to affect their coordinate repression. Here, we show that, in contrast to its direct repression of exon 4, hnRNP L represses exon 5 by countering the activity of a neighboring splicing enhancer. In the absence of the enhancer, hnRNP L unexpectedly activates exon inclusion. As the splice sites flanking exon 4 and 5 are distinct, we directly examined the effect of varying splice site strength on the mechanism of hnRNP L function. Remarkably, binding of hnRNP L to an exon represses strong splice sites but enhances weak splice sites. A model in which hnRNP L stabilizes snRNP binding can explain both effects in a manner determined by the inherent snRNP-substrate affinity.

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Citations

Sep 2, 2010·Nucleic Acids Research·Sergio Barberan-SolerAlan M Zahler
Nov 20, 2012·Nucleic Acids Research·Suresh PeddigariSandra L Martin
Mar 10, 2012·Nucleic Acids Research·Marco PreussnerAlbrecht Bindereif
Mar 30, 2011·Molecular and Cellular Biology·Michael J MalloryKristen W Lynch
Oct 26, 2010·The Journal of Clinical Investigation·Rachel Wilson GoeheCharles E Chalfant
Mar 29, 2012·RNA·Nicole M MartinezKristen W Lynch
Aug 13, 2014·Nature Reviews. Genetics·Xiang-Dong Fu, Manuel Ares
Feb 12, 2013·The Journal of Biological Chemistry·Ngoc T VuCharles E Chalfant
Dec 26, 2015·International Journal of Molecular Sciences·Mehmet YabasGerard F Hoyne
Oct 15, 2013·Scientific Reports·Mohammad Alinoor RahmanKinji Ohno
Jun 15, 2013·Wiley Interdisciplinary Reviews. RNA·Sali Liu, Chonghui Cheng
Apr 14, 2016·Nature Communications·Isabel MeiningerDaniel Krappmann
Jan 28, 2015·Biochimica Et Biophysica Acta·Tiing Jen LohHaihong Shen
Aug 28, 2010·The Biochemical Journal·Siew Ping HanRoss Smith
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Mar 25, 2014·RNA Biology·Michela RaponiDiana Baralle
Mar 1, 2012·Molecular Cell·Xiong Ji, Xiang-Dong Fu
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Jul 30, 2019·EMBO Reports·Yoshihiro KawasakiTetsu Akiyama
Mar 9, 2017·The Biochemical Journal·Sathiya Pandi NarayananSanjeev Shukla

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