Dephosphorylation shows SR proteins the way out

Abstract

To address the role of the RS domain in shuttling and how it is differentially required for constitutive and alternative splicing, Lin et al. (2005 [in the November 11 issue of Molecular Cell]) employ an elegant somatic complementation system to reveal a novel phosphorylation-dependent mechanism regulating distinct recycling pathways for SR proteins during mRNP maturation.

Figure 1. Distinct Recycling Pathways for SR Proteins During mRNP Maturation

SR shuttling proteins (left half) are phosphorylated by a putative kinase (orange). This phosphorylation is important during mRNP maturation within the nucleus. However, when these SR-mRNA complexes are to be exported, a putative phosphatase removes the phosphorylation from the RS domain, which allows for proper shuttling and export to the cytosol, probably with the association of additional factors. In contrast, nonshuttling SR proteins (right half), while phosphorylated by the same or a different putative kinase, may undergo two potential modifications. It is possible that the RS domain or other portions of the protein undergo a conformational change that renders it phosphatase resistant or that allows a cofactor (green) to bind to the phosphorylated protein, blocking access to the phosphatase. Whatever the mechanism, this phosphate tags the SR protein for nuclear retention and recycling.