Role of Ser-Arg Proteins in the Regulation of RNA Processing.
Abstract
Deregulation of alternative splicing has been linked to malignant transformation in breast cancers. Therefore, to fully understand breast cancer, it will be important to identify and characterize factors that regulate the splicing process. Nuclear matrix proteins (NMp's) containing serine/arginine (SR)-rich domains that associate with splicing complexes were isolated and characterized. The NMp's BlC8 (l6OkDa) and B4Al 1 (3OOkDa) are novel SR phosphoproteins of 820 and 2245 amino acids, respectively. Unlike previously defined SR family proteins (SRp's), which function as constitutive and regulatory splicing factors, B lC8 and B4Al 1 lack RNA Recognition Motifs (RRMs). B lC8 and B4Al 1 form a complex (BlC8iB4All) that associates with SR family proteins SRp4O and SRp75. BlC8/B4All is required for the splicing of a subset of pre-IriRNAs in vitro. BlC8/B4A1 1 binds to pre-mRNA and promotes splicing in combination with SR family proteins. The association of B 1C8/B4A1 1 with pre-mRNA also requires binding of U 1 snRNP to the 5' splice site and is stabilized by binding of U2 snRNP to the branch site. Thus, B 1C8/B4A1 1 appears to form critical interactions that span intron sequences. These results suggest that B 1C8/B4A1 I functions as a splicing "coactivator", by augmenting the activity of factors bound to pre-mRNA. These results are providing new insights into mechanisms by which pre-rnRNA splicing may be regulated.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1997
- Accession Number
- ADA339302
Entities
People
- Benjamin J. Blencowe
Organizations
- Massachusetts Institute of Technology