Abstract
In this chapter, experiments will be reviewed which lead from the initial hypothesis of the role of protein phosphorylation in pre-mRNA splicing to the elucidation of mechanism(s) by which this modification alters the function of splicing factors. Phosphorylation has been implicated in the assembly of the spliceosome (Tazi et al. 1992; Mermoud et al. 1994a), regulation of splice site selection (Du et al. 1998; Xiao and Manley 1998; Prasad et al. 1999; Stojdl and Bell 1999; Pilch et al. 2001) and subcellular localization of splicing factors (Misteli and Spector 1996; Misteli et al. 1998). Several splicing factors are known to be phosphorylated in vivo, including a number of the serine/ arginine-rich (SR) protein family (Fu 1995; Graveley 2000), protein components of the small nuclear ribonucleoproteins (snRNPs; Tazi et al. 1993; Woppmann et al. 1993; Fetzer et al. 1997) and proteins associated with the spliceosome (SAPs; Gozani et al. 1994; Chiara et al. 1996; Reed 1996). Phosphorylation and dephosphorylation of these factors might act as a modulator of protein-protein (Xiao and Manley 1997) and protein-RNA interactions at multiple stages during the biogenesis of mRNAs (Tazi et al. 1997). A major advance towards understanding the regulation of pre-mRNA splicing by protein phosphorylation has been to isolate and characterize potential protein kinases and phosphatases that specifically target components of the splicing apparatus. We will review the molecular components of the splicing machinery which are affected by phosphorylation and consider the mechanisms by which specific kinases and phosphatases seem to contribute to a dynamic organization of pre-mRNA splicing factory, not only during transcription, but also in response to physiological stimuli.
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Soret, J., Tazi, J. (2003). Phosphorylation-Dependent Control of the Pre-mRNA Splicing Machinery. In: Jeanteur, P. (eds) Regulation of Alternative Splicing. Progress in Molecular and Subcellular Biology, vol 31. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-09728-1_4
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DOI: https://doi.org/10.1007/978-3-662-09728-1_4
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