Identification and characterization of the CDK12/cyclin L1 complex involved in alternative splicing regulation

Molecular and Cellular Biology
Hung-Hsi ChenMing-Ji Fann

Abstract

CrkRS is a Cdc2-related protein kinase that contains an arginine- and serine-rich (SR) domain, a characteristic of the SR protein family of splicing factors, and is proposed to be involved in RNA processing. However, whether it acts together with a cyclin and at which steps it may function to regulate RNA processing are not clear. Here, we report that CrkRS interacts with cyclin L1 and cyclin L2, and thus rename it as the long form of cyclin-dependent kinase 12 (CDK12(L)). A shorter isoform of CDK12, CDK12(S), that differs from CDK12(L) only at the carboxyl end, was also identified. Both isoforms associate with cyclin L1 through interactions mediated by the kinase domain and the cyclin domain, suggesting a bona fide CDK/cyclin partnership. Furthermore, CDK12 isoforms alter the splicing pattern of an E1a minigene, and the effect is potentiated by the cyclin domain of cyclin L1. When expression of CDK12 isoforms is perturbed by small interfering RNAs, a reversal of the splicing choices is observed. The activity of CDK12 on splicing is counteracted by SF2/ASF and SC35, but not by SRp40, SRp55, and SRp75. Together, our findings indicate that CDK12 and cyclin L1/L2 are cyclin-dependent kinase and cyclin partners and regulate alterna...Continue Reading

References

Nov 8, 1994·Proceedings of the National Academy of Sciences of the United States of America·J F GuiX D Fu
Jan 1, 1995·Molecular and Cellular Biology·J M LahtiV J Kidd
Jul 22, 1998·Nucleic Acids Research·O NaylerS Stamm
Apr 15, 2000·Cellular and Molecular Life Sciences : CMLS·A V Philips, T A Cooper
Jan 11, 2000·Nucleic Acids Research·W van Der Houven Van OordtJ F Cáceres
Feb 13, 2001·Biochemical and Biophysical Research Communications·F MarquésA M Genevière
Mar 10, 2001·Nature·A W Murray, D Marks
Mar 10, 2001·Nature·E S LanderUNKNOWN International Human Genome Sequencing Consortium
Apr 25, 2002·Proceedings of the National Academy of Sciences of the United States of America·Jenn-Yah YuDavid L Turner
May 1, 2002·The Journal of Biological Chemistry·Liliane A DickinsonJoel M Gottesfeld
Jul 12, 2002·Nature·Tom Maniatis, Bosiljka Tasic
Dec 27, 2002·The Journal of Biological Chemistry·Dongli HuVincent J Kidd
May 4, 2004·Nature Biotechnology·Mariano A Garcia-BlancoErika L Lasda
Sep 2, 2004·Nature Reviews. Molecular Cell Biology·Chanseok Shin, James L Manley
Oct 22, 2004·Nature·UNKNOWN International Human Genome Sequencing Consortium
Nov 3, 2004·Cancer Research·Julian P Venables
Jun 7, 2005·Cellular Signalling·Pascal LoyerJill M Lahti

❮ Previous
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Citations

Mar 19, 2013·Archives of Gynecology and Obstetrics·Susanne SchülerOlaf Ortmann
Mar 27, 2007·Journal of Biomedical Science·Woan-Yuh Tarn
Jan 16, 2009·Molecular Biotechnology·John H Doonan, Georgios Kitsios
Jul 2, 2011·Nature·UNKNOWN Cancer Genome Atlas Research Network
Nov 4, 2009·Nature Cell Biology·Marcos MalumbresDebra J Wolgemuth
Feb 25, 2009·Nature Reviews. Cancer·Marcos Malumbres, Mariano Barbacid
Aug 5, 2009·Carcinogenesis·Elizabeth IornsAlan Ashworth
Oct 19, 2010·Genes & Development·Bartlomiej BartkowiakArno L Greenleaf
May 14, 2009·The Journal of Clinical Investigation·Ariane ChapgierJean-Laurent Casanova
Jan 30, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·S D YogeshaYan Zhang
Jan 1, 2011·Genetics Research International·Bartlomiej BartkowiakArno L Greenleaf
Jan 30, 2013·Pharmacology & Therapeutics·Santiago Diaz-MoralliMarta Cascante
May 19, 2011·Biochemical and Biophysical Research Communications·Li PengZhang Xichen
Feb 16, 2016·Journal of Molecular Biology·Célia JeronimoFrançois Robert
Dec 15, 2015·Cell Death and Differentiation·H-C JuanM-J Fann
Feb 9, 2008·Biochimica Et Biophysica Acta·Jiuyong Xie
Jan 31, 2007·Biochemical and Biophysical Research Communications·Hung-Hsi ChenMing-Ji Fann
Jan 9, 2007·Current Opinion in Genetics & Development·Marcos Malumbres, Mariano Barbacid
Nov 28, 2012·Wiley Interdisciplinary Reviews. RNA·Tina Lenasi, Matjaz Barboric
Sep 14, 2010·Journal of Cellular Physiology·Józefa Węsierska-GądekOxana Komina
Jun 24, 2015·Experimental Neurology·Ting-Ya Chang, Pei-Lin Cheng
Apr 5, 2011·Cellular & Molecular Biology Letters·Vladan P BajićXiongwei Zhu
Nov 3, 2006·Developmental Biology·Antonio Fernandez-GuerraAnne-Marie Genevière
Aug 30, 2016·Nature Chemical Biology·Tinghu ZhangNathanael S Gray
Jan 6, 2009·International Journal of Molecular Sciences·Sissada TannukitMichael L Paine
Apr 24, 2018·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Liliana Krasinska, Daniel Fisher
Jun 3, 2006·Journal of Cellular Biochemistry·Luigi BagellaAntonio Giordano
May 15, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Andreas HerrmannWalter Becker

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