Accession Number:

ADA339302

Title:

Role of Ser-Arg Proteins in the Regulation of RNA Processing.

Descriptive Note:

Annual rept. 1 Sep 96-31 Aug 97.

Corporate Author:

MASSACHUSETTS INST OF TECH CAMBRIDGE

Personal Author(s):

Report Date:

1997-09-01

Pagination or Media Count:

36.0

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 NMps containing serinearginine SR-rich domains that associate with splicing complexes were isolated and characterized. The NMps BlC8 l6OkDa and B4Al 1 3OOkDa are novel SR phosphoproteins of 820 and 2245 amino acids, respectively. Unlike previously defined SR family proteins SRps, 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. BlC8B4All is required for the splicing of a subset of pre-IriRNAs in vitro. BlC8B4A1 1 binds to pre-mRNA and promotes splicing in combination with SR family proteins. The association of B 1C8B4A1 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 1C8B4A1 1 appears to form critical interactions that span intron sequences. These results suggest that B 1C8B4A1 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.

Subject Categories:

  • Biochemistry
  • Anatomy and Physiology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE