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First published online 22 February 2005
doi: 10.1242/jcs.01720

Journal of Cell Science 118, 1151-1159 (2005)
Published by The Company of Biologists 2005
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Research Article

Stress alters the subcellular distribution of hSlu7 and thus modulates alternative splicing

Noam Shomron*, Moti Alberstein*, Mika Reznik and Gil Ast{ddagger}

Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Tel Aviv, Israel

{ddagger} Author for correspondence (e-mail: gilast{at}post.tau.ac.il)

Accepted 18 January 2005

During pre-mRNA splicing, introns are removed and exons are ligated to form an mRNA. Exon choice is determined by different nuclear protein concentrations varying among tissues and cell types or by developmental stage. These can be altered by different cellular circumstances such as physiological stimuli, environmental effects and phosphorylation state. The splicing factor hSlu7 plays an important role in 3' splice site selection during the second step of splicing in vitro and has been suggested to affect alternative splicing in vivo. Our results indicate that an ultraviolet-C (UV-C) stress stimulus triggers changes in the alternative splicing patterns of cellular genes by decreasing the nuclear concentration of hSlu7 through the modulation of its nucleus-to-cytoplasm transport. This shift is mostly dependent on the Jun N-terminal kinase (JNK) cascade. Although we found by RNAi knockdown that hSlu7 is not essential for cell viability, its nuclear concentration effects exon choice and inclusion:skipping ratio of alternative splicing. A possible spatial and temporal regulatory mechanism by which hSlu7 protein levels are regulated within the nucleus is suggested, thus implying a broad effect of hSlu7 on alternative splicing.

Key words: hSlu7, mRNA splicing, Nuclear-cytoplasmic shift, Stress, Cellular localization, Alternative splicing, Spliceosome, snRNP




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