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Reprogramming Alternative Pre-messenger RNA Splicing through the Use of Protein-binding Antisense Oligonucleotides*
 

Summary: Reprogramming Alternative Pre-messenger RNA Splicing through
the Use of Protein-binding Antisense Oligonucleotides*
Received for publication, August 12, 2003, and in revised form, September 25, 2003
Published, JBC Papers in Press, September 30, 2003, DOI 10.1074/jbc.M308897200
Jonathan Villemaire, Isabelle Dion, Sherif Abou Elela§, and Benoit Chabot¶
From the De´partement de microbiologie et d'infectiologie, RNA/RNP Group, Faculte´ de Me´decine, Universite´ de
Sherbrooke, Sherbrooke, Que´bec J1H 5N4, Canada
Alternative pre-messenger RNA splicing is a major
contributor to proteomic diversity in higher eukaryotes
and represents a key step in the control of protein func-
tion in a large variety of biological systems. As a means
of artificially altering splice site choice, we have inves-
tigated the impact of positioning proteins in the vicinity
of 5 splice sites. We find that a recombinant GST-MS2
protein interferes with 5 splice site use, most efficiently
when it binds upstream of that site. To broaden the use
of proteins as steric inhibitors of splicing, we have
tested the activity of antisense oligonucleotides carry-
ing binding sites for the heterogeneous nuclear ribonu-
cleoprotein A1/A2 proteins. In a HeLa cell extract, tailed

  

Source: Abou Elela, Sherif - Département de Microbiologie et d'Infectiologie, Université de Sherbrooke

 

Collections: Biology and Medicine