Auto- and cross-regulation of the hnRNP L proteins by alternative splicing.

Molecular and Cellular Biology
Oliver RossbachAlbrecht Bindereif

Abstract

We recently characterized human hnRNP L as a global regulator of alternative splicing, binding to CA-repeat and CA-rich elements. Here we report that hnRNP L autoregulates its own expression on the level of alternative splicing. Intron 6 of the human hnRNP L gene contains a short exon that, if used, introduces a premature termination codon, resulting in nonsense-mediated decay (NMD). This "poison exon" is preceded by a highly conserved CA-rich cluster extending over 800 nucleotides that binds hnRNP L and functions as an unusually extended, intronic enhancer, promoting inclusion of the poison exon. As a result, excess hnRNP L activates NMD of its own mRNA, thereby creating a negative autoregulatory feedback loop and contributing to homeostasis of hnRNP L levels. We present experimental evidence for this mechanism, based on NMD inactivation, hnRNP L binding assays, and hnRNP L-dependent alternative splicing of heterologous constructs. In addition, we demonstrate that hnRNP L cross-regulates inclusion of an analogous poison exon in the hnRNP L-like pre-mRNA, which explains the reciprocal expression of the two closely related hnRNP L proteins.

References

Dec 1, 1989·The Journal of Cell Biology·S Piñol-RomaG Dreyfuss
Oct 29, 1997·Molecular and Cellular Biology·E F Modafferi, D L Black
Aug 1, 2000·Trends in Biochemical Sciences·C W Smith, J Valcárcel
Dec 26, 2001·Nature Genetics·Barmak Modrek, Christopher Lee
Apr 23, 2002·Nature Reviews. Genetics·Luca CartegniAdrian R Krainer
Nov 26, 2002·Nature Structural Biology·Jingyi HuiAlbrecht Bindereif
Mar 11, 2003·Annual Review of Biochemistry·Douglas L Black
Jul 19, 2003·RNA·Jingyi HuiAlbrecht Bindereif
Aug 3, 2004·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Gene Yeo, Christopher B Burge
Sep 2, 2004·Nature Reviews. Molecular Cell Biology·Chanseok Shin, James L Manley
Jun 16, 2005·Nature Reviews. Molecular Cell Biology·Arianne J MatlinChristopher W J Smith
Jul 8, 2005·The EMBO Journal·Caryn R RothrockKristen W Lynch
Jul 15, 2006·Cell·Benjamin J Blencowe
Sep 26, 2006·Nature Structural & Molecular Biology·Amy E House, Kristen W Lynch
Jul 4, 2007·Genes & Development·Gabriela C Coutinho-MansfieldXiang-Dong Fu
Aug 1, 2007·Molecular and Cellular Biology·Alexis A MeltonKristen W Lynch
Nov 21, 2007·The Journal of Biological Chemistry·Claudia Ben-DovJuan Valcárcel
Mar 29, 2008·Science·Eugene V Makeyev, Tom Maniatis
Apr 30, 2008·Molecular and Cellular Biology·Arneet L SaltzmanBenjamin J Blencowe

❮ Previous
Next ❯

Citations

Jun 18, 2011·Journal of Molecular Neuroscience : MN·Mauricio Budini, Emanuele Buratti
May 8, 2013·Trends in Genetics : TIG·Sika Zheng, Douglas L Black
Mar 10, 2012·Nucleic Acids Research·Marco PreussnerAlbrecht Bindereif
Feb 18, 2011·Genes & Development·Arneet L SaltzmanBenjamin J Blencowe
Dec 18, 2010·Genome Research·Joanna Y IpBenjamin J Blencowe
Apr 6, 2012·PLoS Genetics·Alex M Plocik, Christine Guthrie
Oct 23, 2013·PLoS Genetics·Tanja Dorothe Rösel-HillgärtnerAlbrecht Bindereif
Apr 15, 2015·Proceedings of the National Academy of Sciences of the United States of America·Michael J MalloryKristen W Lynch
Mar 13, 2016·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Sika Zheng
Mar 11, 2016·Nucleic Acids Research·Satomi TakeiHidehito Kuroyanagi
Nov 25, 2014·Cell·Mohini Jangi, Phillip A Sharp
Dec 7, 2010·The EMBO Journal·Youhna M AyalaFrancisco E Baralle
Aug 28, 2010·The Biochemical Journal·Siew Ping HanRoss Smith
Aug 12, 2014·Biochemical Society Transactions·Christopher R Sibley
May 3, 2015·Biochimica Et Biophysica Acta·Dairong FengJiuyong Xie
May 6, 2015·Nucleic Acids Research·Lit-Yeen TanChristopher W J Smith
Mar 25, 2014·RNA Biology·Michela RaponiDiana Baralle
Apr 4, 2015·Current Opinion in Plant Biology·Sergei FilichkinTodd C Mockler
Jun 1, 2016·Nature Reviews. Genetics·Christopher R SibleyJernej Ule
Sep 26, 2016·Journal of Mathematical Biology·Pavol Bokes, Abhyudai Singh
Oct 15, 2013·Scientific Reports·Mohammad Alinoor RahmanKinji Ohno
Nov 29, 2017·The Journal of Biological Chemistry·Akira HashiramotoShunichi Shiozawa
Mar 28, 2018·RNA·Sean P McCloryJonathan P Ling
Dec 17, 2014·Molecular and Cellular Biology·Agnès MéreauLuc Paillard
Oct 30, 2013·Molecular and Cellular Biology·Ganesh ShankarlingKristen W Lynch
Sep 28, 2017·RNA Biology·Patryk KoniecznyKrzysztof Sobczak
Jan 27, 2019·The EMBO Journal·Miles F Wilkinson, Heidi Cook-Andersen
Jun 4, 2019·Journal of Molecular Cell Biology·Michaela Müller-McNicollJan Medenbach

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alternative splicing

Alternative splicing a regulated gene expression process that allows a single genetic sequence to code for multiple proteins. Here is that latest research.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.