Concerted regulation of nuclear and cytoplasmic activities of SR proteins by AKT

BLAUSTEIN, M; PELISCH, F; TANOS, T; MUÑOZ, M; SANFORD, J; WENGIER, D; QUADRANA, L; MUSCHIETTI, J; KORNBLIHTT, A; CÁCERES, J; COSO, O; SREBROW, A

NATURE STRUCTURAL & MOLECULAR BIOLOGY

NATURE PUBLISHING GROUP

Año: 2005 vol. 12 p. 1037 - 1045

1545-9985

Serine/Arginine-rich (SR) proteins are important regulators of mRNA splicing. Recently, several post-splicing activities have been described for a subset of shuttling SR proteins, including regulation of mRNA export and translation. Using the fibronectin (FN) gene to study the linkage between signal transduction pathways and the activities of SR proteins, we show that growth factors (GFs) not only modify the alternative splicing pattern of the FN gene but also alter translation of reporter mRNAs in an SR protein-dependent fashion, providing two co-regulated levels of isoform-specific amplification. These effects are inhibited by specific small interfering RNAs (siRNAs) against SR proteins and are mediated by the AKT kinase, which elicits opposite effects to those evoked by SR protein kinases Clk/Sty and SRPK. These results show how SR protein activity is modified in response to extracellular stimulation leading to a concerted regulation of splicing and translation.