Role of Nuclear Matrix Proteins in the Regulation of Pre-mRNA Splicing
Abstract
Deregulation of 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 related to the serine/arginine-rich (SR) family of constitutive and regulatory splicing factors were isolated and characterized. B1C8 is a novel 820 amino acid SR phosphoprotein that, unlike previously defined SR family proteins, lacks an RNA Recognition Motif (RRM). B1C8 and a second novel SR phosphoprotein, B4A11 (300kDa), associate with each other and with splicing complexes through both steps of the splicing reaction. However, B1C8/B4A11 is required for splicing of only specific introns. Purified B1C8/B4A11 promotes splicing synergistically when added in combination with SR family proteins. B1C8/B4A11 may therefore function as a splicing 'coactivator' by augmenting the activity of SR family proteins. The absence of an RRM in B1C8 further suggests that it may define a new class of SR protein factors that promotes splicing primarily through protein-protein interactions. These results provide new insights into mechanisms by which pre-mRNA splicing may be regulated.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1996
- Accession Number
- ADB222794
Entities
People
- Benjamin J. Blencowe
Organizations
- Massachusetts Institute of Technology