TDP BindsHeterogeneousNuclearRibonucleoproteinAB…结合非均相核糖核蛋白.pdfVIP

THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 280, NO. 45, pp. 37572–37584, November 11, 2005 © 2005 by The American Society for Biochemistry and Molecular Biology, Inc. Printed in the U.S.A. TDP-43 Binds Heterogeneous Nuclear Ribonucleoprotein A/B through Its C-terminal Tail AN IMPORTANT REGION FOR THE INHIBITION OF CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR EXON 9 SPLICING* Received for publication, May 20, 2005, and in revised form, September 7, 2005 Published, JBC Papers in Press, September 12, 2005, DOI 10.1074/jbc.M505557200 Emanuele Buratti1 1 , Antonia Brindisi , Maurizio Giombi, Sergio Tisminetzky, Youhna M. Ayala, and Francisco E. Baralle2 From the International Centre for Genetic Engineering and Biotechnology, 34012 Trieste, Italy TDP-43 is a highly conserved nuclear factor of yet unknown func- when, where, and to what degree a specific sequence will be included or tion that binds to ug-repeated sequences and is responsible for cys- not in the mature mRNA (17). Recently, the finding that at least 5% of all tic fibrosis transmembrane conductance regulator exon 9 splicing human alternative exons are derived from the highly repeated dimeric inhibition. We have analyzed TDP-43 interactions with other splic- retrotransposons Alu elements has focused a lot of attention on the ing factors and identified the critical regions for the protein/protein potential splicing modulatory ability of repeated nucleotide sequences recognition events that determine this biological function. We show (21).