Three proteins, MBNL, MBLL and MBXL, co-localize in vivo with nuclear foci of expanded-repeat transcripts in DM1 and DM2 cells

Human Molecular Genetics
Majid FardaeiJ David Brook

Abstract

Myotonic dystrophy is a complex neuromuscular disorder associated with DNA expansion mutations in two different genes. In DM1 a CTG repeat in the 3'-untranslated region of DMPK is expanded, whereas in DM2 an intronic CCTG expansion occurs in the gene ZNF9. Transcripts containing expanded repeats form foci in the nuclei of DM1 and DM2 cells. Recent work using antibodies has shown that proteins related to Drosophila muscleblind co-localize with repeat foci in DM1 and DM2 cells. We show that rather than there being a single human muscleblind gene producing multiple proteins through alternative splicing, there are in fact three different muscleblind genes, MBNL, MBLL and MBXL, which map to chromosomes 3, 13 and X, respectively, and which show extensive alternative splicing. Two of the genes, MBNL and MBLL, are expressed in many adult tissues whereas MBXL is expressed predominantly in the placenta. Green fluorescent protein-tagged versions of MBNL, MBLL and MBXL co-localize with nuclear foci in DM1 and DM2 cells, suggesting that all three proteins may play a role in DM pathophysiology.

Citations

Sep 26, 2002·Developmental Biology·Rachel M SquillaceEdith H Wang
Jul 14, 2011·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Christopher R Sibley, Matthew J A Wood
Jan 6, 2012·Analytical and Bioanalytical Chemistry·Catherine Z ChenChristopher P Austin
Mar 10, 2011·Histochemistry and Cell Biology·Manuela MalatestaCarlo Pellicciari
Mar 28, 2009·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Sergio SalvatoriCorrado Angelini
Nov 11, 2009·Bulletin of Experimental Biology and Medicine·E A Tonevitsky, E V Trushkin
Aug 10, 2002·Current Neurology and Neuroscience Reports·Laura P W Ranum, John W Day
Jan 29, 2005·Current Neurology and Neuroscience Reports·John W Day, Laura P W Ranum
Feb 25, 2003·The American Journal of Pathology·Denis FurlingGlenn E Morris
Aug 14, 2003·Gene Expression Patterns : GEP·Rahul N KanadiaMaurice S Swanson
Jun 19, 2008·Biochemistry·Emily S GoersJ Andrew Berglund
Jan 29, 2009·European Journal of Human Genetics : EJHG·R P Junghans
Oct 8, 2009·European Journal of Human Genetics : EJHG·Annemieke Aartsma-Rus, Gert-Jan B van Ommen
Dec 2, 2008·Nature Structural & Molecular Biology·Marianna Teplova, Dinshaw J Patel
Jan 26, 2010·Nature Structural & Molecular Biology·Hongqing DuManuel Ares
Feb 15, 2008·Proceedings of the National Academy of Sciences of the United States of America·James P OrengoThomas A Cooper
Oct 14, 2009·Proceedings of the National Academy of Sciences of the United States of America·M Bryan WarfJ Andrew Berglund
Aug 17, 2010·The Journal of Biological Chemistry·Kyung-Soon LeeEdith H Wang
Aug 13, 2011·The Journal of Biological Chemistry·Devika P GatesJ Andrew Berglund
Sep 29, 2011·The Journal of Biological Chemistry·Erin B HarmonM Benjamin Perryman
Feb 19, 2009·Human Molecular Genetics·Robert J OsborneCharles A Thornton
Apr 22, 2010·Human Molecular Genetics·Susan A M MuldersDerick G Wansink
Jul 7, 2011·Human Molecular Genetics·Marzena Wojciechowska, Wlodzimierz J Krzyzosiak
Aug 9, 2011·Human Molecular Genetics·Géraldine SicotMário Gomes-Pereira
May 11, 2013·Human Molecular Genetics·Michael G PoulosMaurice S Swanson
Sep 23, 2003·Nucleic Acids Research·Krzysztof SobczakWlodzimierz J Krzyzosiak
Sep 23, 2003·Nucleic Acids Research·Anna JasinskaWlodzimierz J Krzyzosiak
Aug 19, 2007·Nucleic Acids Research·Yuan YuanMaurice S Swanson
May 13, 2009·Nucleic Acids Research·Agnieszka KiliszekWojciech Rypniewski
Nov 27, 2010·Nucleic Acids Research·Ioannis GrammatikakisThomas A Cooper
Apr 15, 2011·Biological Reviews of the Cambridge Philosophical Society·Juan M Fernandez-CostaRuben Artero
Aug 15, 2012·Molecular and Cellular Biology·Jamie PurcellJ Andrew Berglund
Dec 5, 2008·Microbiology and Molecular Biology Reviews : MMBR·Guy-Franck RichardBernard Dujon
Jun 17, 2006·Annual Review of Neuroscience·Laura P W Ranum, Thomas A Cooper
Nov 13, 2009·The Journal of Clinical Investigation·Guey-Shin WangThomas A Cooper

❮ 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.