Stop codon-mediated suppression of splicing is a novel nuclear scanning mechanism not affected by elements of protein synthesis and NMD

RNA
Chaim WachtelRuth Sperling

Abstract

The pre-mRNA splicing machine must frequently discriminate between normal and many potential 5'splice sites that match the consensus sequence but remain latent. Suppression of splicing (SOS) at such latent 5'splice sites is required for the maintenance of an open reading frame, and to ensure that only RNAs that encode for functional proteins will be formed. In this study we show that SOS is a novel mechanism distinct from the known RNA surveillance mechanisms. First, SOS is distinct from nonsense-mediated mRNA decay (NMD) because it is not dependent on translation and is not affected by RNAi-mediated down-regulation of hUpf1 and hUpf2--two key components of the NMD pathway. Second, SOS is distinct from nonsense-associated alternative splicing (NAS), because a mutant of hUpf1, which was shown to abrogate NAS, does not activate latent splicing. Elucidating the mechanism of SOS is pertinent to human disease in view of the large number of human genes that harbor latent splice sites.

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Citations

Oct 4, 2005·RNA·Patricia A Schroder, Melissa J Moore
Jul 21, 2006·Nucleic Acids Research·Eyal KamhiJoseph Sperling
Mar 26, 2008·Proceedings of the National Academy of Sciences of the United States of America·Lily AgranatRuth Sperling
Dec 17, 2009·Nucleic Acids Research·J Saadi ImamMiles F Wilkinson
Jul 14, 2011·Genome Research·Timothy Sterne-WeilerJeremy R Sanford
Sep 25, 2012·Nucleic Acids Research·Yuval NevoRuth Sperling
May 20, 2005·Current Opinion in Cell Biology·Fabrice Lejeune, Lynne E Maquat
Nov 20, 2014·Computational and Structural Biotechnology Journal·Kinneret SheferRuth Sperling
Jun 11, 2010·Proceedings of the National Academy of Sciences of the United States of America·Eyal KamhiJoseph Sperling
Jan 19, 2008·Nature·Olivier JaillonEric Meyer
Dec 22, 2005·Molecular Biology and Evolution·Feng-Chi ChenTrees-Juen Chuang
Aug 3, 2007·Genes & Development·Olaf Isken, Lynne E Maquat

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