A Proteomic Strategy Identifies Lysine Methylation of Splicing Factor snRNP70 by the SETMAR Enzyme.

The Journal of Biological Chemistry
Scott M CarlsonOr Gozani

Abstract

The lysine methyltransferase (KMT) SETMAR is implicated in the response to and repair of DNA damage, but its molecular function is not clear. SETMAR has been associated with dimethylation of histone H3 lysine 36 (H3K36) at sites of DNA damage. However, SETMAR does not methylate H3K36 in vitro. This and the observation that SETMAR is not active on nucleosomes suggest that H3K36 methylation is not a physiologically relevant activity. To identify potential non-histone substrates, we utilized a strategy on the basis of quantitative proteomic analysis of methylated lysine. Our approach identified lysine 130 of the mRNA splicing factor snRNP70 as a SETMAR substrate in vitro, and we show that the enzyme primarily generates monomethylation at this position. Furthermore, we show that SETMAR methylates snRNP70 Lys-130 in cells. Because snRNP70 is a key early regulator of 5' splice site selection, our results suggest a model in which methylation of snRNP70 by SETMAR regulates constitutive and/or alternative splicing. In addition, the proteomic strategy described here is broadly applicable and is a promising route for large-scale mapping of KMT substrates.

References

Dec 14, 2004·The Journal of Biological Chemistry·Robert E CollinsXiaodong Cheng
Aug 10, 2005·Genome Biology·Shane C DillonXiaodong Cheng
Dec 8, 2005·Proceedings of the National Academy of Sciences of the United States of America·Suk-Hee LeeRobert Hromas
May 5, 2006·Proceedings of the National Academy of Sciences of the United States of America·Richard CordauxCédric Feschotte
Apr 5, 2007·Nature Protocols·Shao-En Ong, Matthias Mann
Apr 21, 2007·Nature Protocols·Benjamin A GarciaDonald F Hunt
May 9, 2007·Methods in Molecular Biology·Shao-En Ong, Matthias Mann
Feb 12, 2008·The Journal of Biological Chemistry·Brian D BeckSuk-Hee Lee
Jan 20, 2009·Molecular Cell·Mark T Bedford, Steven G Clarke
May 22, 2009·Blood·Justin WrayRobert Hromas
May 12, 2010·Nucleic Acids Research·Leyma P De HaroJac A Nickoloff
Sep 28, 2010·The Journal of Biological Chemistry·Lisandra E WestOr Gozani
Dec 21, 2010·Current Biology : CB·Stephen M FuchsBrian D Strahl
Dec 29, 2010·Proceedings of the National Academy of Sciences of the United States of America·Sheema FnuRobert Hromas
Dec 24, 2011·Acta Biochimica Et Biophysica Sinica·Xi ZhangXiaobing Shi
Sep 6, 2012·Nature Communications·Stefan KernstockPål Ø Falnes
Jan 5, 2013·Science·Le CongFeng Zhang
May 7, 2013·Epigenetics : Official Journal of the DNA Methylation Society·Xing-Jun CaoBenjamin A Garcia
Oct 17, 2013·Molecular & Cellular Proteomics : MCP·Ailan GuoMichael J Comb
Dec 7, 2013·Nature Protocols·Scott M CarlsonOr Gozani
May 9, 2014·Journal of Molecular Biology·Scott M Carlson, Or Gozani
May 30, 2014·Epigenetics & Chromatin·Zhangli SuJohn M Denu
Jul 31, 2014·Nature Methods·Neville E SanjanaFeng Zhang
Dec 17, 2014·Molecular & Cellular Proteomics : MCP·Zhixiang WuYingming Zhao

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Citations

Jan 3, 2016·Drug Discovery Today. Technologies·Kurumi Y Horiuchi
Aug 23, 2016·Future Medicinal Chemistry·David S RogawskiTomasz Cierpicki
Aug 30, 2016·Cell Chemical Biology·Srikanth Kudithipudi, Albert Jeltsch
Oct 18, 2018·Nucleic Acids Research·Michael Tellier, Ronald Chalmers
Oct 5, 2019·Nature Structural & Molecular Biology·Dylan Husmann, Or Gozani
Dec 31, 2016·Oncotarget·Audrey Dussaussois-MontagneCorinne Augé-Gouillou
Aug 10, 2016·Cold Spring Harbor Perspectives in Medicine·Steven Henikoff
Jul 3, 2020·The Journal of Biological Chemistry·Muhammad ZoabiOr Gozani
Nov 3, 2016·Cold Spring Harbor Perspectives in Medicine·Scott M Carlson, Or Gozani
Mar 16, 2017·The FEBS Journal·Zhouran WuKyle K Biggar
Sep 8, 2016·Acta Crystallographica. Section F, Structural Biology Communications·Qiujia Chen, Millie Georgiadis
May 28, 2019·Cellular and Molecular Life Sciences : CMLS·Dan Levy
Jul 6, 2021·The Journal of Biological Chemistry·Ryan J Separovich, Marc R Wilkins

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