Splicing factor HRS/SRp40.

Format:

Book

Thesis/Dissertation

Author/Creator:

Du, Keyong.

Contributor:

University of Pennsylvania.

Language:

English

Subjects (All):

Genetics.

Molecular biology.

0307.

0369.

Local Subjects:

0307.

0369.

Physical Description:

111 pages

Contained In:

Dissertation Abstracts International 58-07B.

System Details:

Mode of access: World Wide Web.

text file

Summary:

HRS/SRp40 is a highly inducible immediate-early gene in insulin-treated H35 rat hepatoma cells and shows a delayed-early induction in regenerating liver. HRS/SRp40 has two different transcripts: 1.7 kb (Short Form) and 2.9 kb (Long Form), which demonstrate different temporal patterns of induction. In this thesis study, I cloned and characterized HRS cDNAs, the mouse HRS gene and partial human HRS gene. We found that HRS/SRp40 belongs to the SR (serine-arginine rich) protein family which regulates both alternative and basal splicing. HRS/SRp40 gene was alternatively spliced to produce HRS-SF and HRS-LF mRNAs. HRS-SF encodes a functional protein and HRS-LF, which contains intron 5, only encodes a truncated HRS protein. HRS expression correlates with the appearance of alternative spliced EIIIB$\sp+$fibronectin transcripts during liver growth. Furthermore, in an in vivo assay, HRS, and not other SR proteins, directly mediates EIIIB exon inclusion in the fibronectin transcript. This alternative splicing is dependent on a purine-rich region within the EIIIB exon to which HRS specifically binds. These studies established that HRS has the potential to contribute to the regulation of fibronectin pre-mRNA splicing during liver growth. We also analyzed the HRS/SRp40 promoter. Two major regulatory proteins, GABP and YY1, were found to regulate HRS gene expression. We demonstrated that while GABP transactivates the HRS/SRp40 promoter YY1 functions as a dominant repressor which not only represses HRS/SRp40 basal promoter activity, but also represses the transactivation of HRS/SRp40 promoter by GABP.

Notes:

Source: Dissertation Abstracts International, Volume: 58-07, Section: B, page: 3466.

Thesis (Ph.D.)--University of Pennsylvania, 1997.

Local Notes:

School code: 0175.

ISBN:

9780591501322

Access Restriction:

Restricted for use by site license.