A novel splicing regulator shares a nuclear import pathway with SR proteins
AUTOR(ES)
Lai, Ming-Chih
FONTE
Oxford University Press
RESUMO
Alternative splicing of precursor mRNA is often regulated by serine/arginine-rich proteins (SR proteins) and hnRNPs, and varying their concentration in the nucleus can be a mechanism for controlling splice site selection. To understand the nucleocytoplasmic transport mechanism of splicing regulators is of key importance. SR proteins are delivered to the nucleus by transportin-SRs (TRN-SRs), importin β-like nuclear transporters. Here we identify and characterize a non-SR protein, RNA-binding motif protein 4 (RBM4), as a novel substrate of TRN-SR2. TRN-SR2 interacts specifically with RBM4 in a Ran-sensitive manner. TRN-SR2 indeed mediates the nuclear import of a recombinant protein containing the RBM4 C-terminal domain. This domain serves as a signal for both nuclear import and export, and for nuclear speckle targeting. Finally, both in vivo and in vitro splicing analyses demonstrate that RBM4 not only modulates alternative pre-mRNA splicing but also acts antagonistically to authentic SR proteins in splice site and exon selection. Thus, a novel splicing regulator with opposite activities to SR proteins shares an identical import pathway with SR proteins to the nucleus.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=151058Documentos Relacionados
- Transportin-SR2 mediates nuclear import of phosphorylated SR proteins
- A Conserved Drosophila Transportin-Serine/Arginine-rich (SR) Protein Permits Nuclear Import of Drosophila SR Protein Splicing Factors and Their Antagonist Repressor Splicing Factor 1
- SR protein splicing factors interact with the Rous sarcoma virus negative regulator of splicing element.
- A complex of nuclear proteins mediates SR protein binding to a purine-rich splicing enhancer.
- Nuclear import of PKCδ is required for apoptosis: identification of a novel nuclear import sequence