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

Matías Blaustein, Federico Pelisch, Tamara Tanos, Manuel J Muñoz, Diego Wengier, Leandro Quadrana, Jeremy R Sanford, Jorge P Muschietti, Alberto R Kornblihtt, Javier F Cáceres, Omar A Coso, Anabella Srebrow

Research output: Contribution to journalArticlepeer-review

Abstract

Serine/arginine-rich (SR) proteins are important regulators of mRNA splicing. Several postsplicing activities have been described for a subset of shuttling SR proteins, including regulation of mRNA export and translation. Using the fibronectin gene to study the links between signal-transduction pathways and SR protein activity, we show that growth factors not only modify the alternative splicing pattern of the fibronectin gene but also alter translation of reporter messenger RNAs in an SR protein-dependent fashion, providing two coregulated levels of isoform-specific amplification. These effects are inhibited by specific small interfering RNAs against SR proteins and are mediated by the AKT kinase, which elicits opposite effects to those evoked by overexpressing SR protein kinases Clk 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.
Original languageEnglish
Pages (from-to)1037-44
Number of pages8
JournalNature Structural & Molecular Biology
Volume12
Issue number12
DOIs
Publication statusPublished - Dec 2005

Keywords

  • Amino Acid Sequence
  • Animals
  • Cell Nucleus
  • Cytoplasm
  • Fibronectins
  • Growth Substances
  • Humans
  • Molecular Sequence Data
  • Nuclear Proteins
  • Phosphatidylinositol 3-Kinases
  • Phosphoproteins
  • Protein Biosynthesis
  • Proto-Oncogene Proteins c-akt
  • RNA Splicing
  • RNA, Messenger
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • Signal Transduction

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