Dephosphorylated SRp38 acts as a splicing repressor in response to heat shock

March 16, 2004

Yi-Chiao, Fang

Abstract

The cellular response to stresses such as heat shock involves changes in gene expression. It is well known that the splicing of messenger RNA precursors is generally repressed on heat shock, but the factors responsible have not been identified. SRp38 is an SR protein splicing factor that functions as a general repressor of splicing. It is activated by dephosphorylation and required for splicing repression in M-phase cells. Here we show that SRp38 is also dephosphorylated on heat shock and that this dephosphorylation correlates with splicing inhibition. We further show that dephosphorylated SRp38 interacts with a U1 small nuclear ribonucleoprotein particle (snRNP) protein, and that this interaction interferes with 5’-splice-site recognition by the U1 snRNP. SRp38 thus plays a crucial role in cell survival under stress conditions by inhibiting the splicing machinery.

Source

Nature. 2004 Feb 5;427(6974):553-8.

Dephosphorylated SRp38 acts as a splicing repressor in response to heat shock.

Chanseok Shin, Ying Feng & James L. Manley.

Reference

1. Shin, C. & Manley, J. L. The SR protein SRp38 represses splicing in M phase cells. Cell 111, 407–417 (2002).

2. Blencowe BJ. Splicing regulation: the cell cycle connection. Curr Biol. 13, 149-151 (2003).

3. Manley, J. M. & Tacke, R. SR proteins and splicing control. Genes Dev. 10, 1569–1579 (1996).

4. Shukla, R. R., Dominiski, Z., Zwierzynski, T. & Kole, R. Inactivation of splicing factors in HeLa cells subjected to heat shock. J. Biol. Chem. 265, 20377–20383 (1990).

5. Xiao, S. H. & Manley, J. L. Phosphorylation–dephosphorylation differentially affects activities of splicing factor ASF/SF2. EMBO J. 17, 6359–6367 (1998).

6. Kohtz, J. D. Protein–protein interactions and 5’-splice-site recognition in mammalian mRNA precursors. Nature 368, 119–124 (1994).