Toggle Main Menu Toggle Search

ePrints

Alternative splicing of the adenylyl cyclase stimulatory G-protein Gαs is regulated by SF2/ASF and heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) and involves the use of an unusual TG 3′-splice site

Lookup NU author(s): Dr Alison Tyson-Capper, Professor Stephen Robson, Professor Nick Europe-Finner

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Abstract

The factors involved in regulating alternative splicing of the human adenylyl cyclase stimulatory G-protein Gαs in different cell types remain undefined. We have designed a Gαs minigene that retains the signals required for Gαs alternative splicing in vivo. Employing transient transfection of human myometrial smooth muscle cells and HeLa cells, as well as in vitro splicing assays, we have provided evidence that the antagonistic splicing factors SF2/ASF and hnRNPA1 act as potent regulators of Gαs isoform expression in these cells. Both SF2/ASF and hnRNPA1 control the selection of competing 5′-splice sites and respectively promote inclusion or skipping of the small cassette-type exon 3 of Gαs transcripts, resulting in the generation of Gαs-long and Gαs-short mRNA isoforms. We have also provided evidence that SF2/ASF and hnRNPA1 play a role in 3′-splice site selection involving the use of a non-canonical TG 3′-splice site preceding exon 4. Using a score-matrix analysis to identify putative exonic enhancer sequences (ESEs), we found multiple high score ESE motifs for SF2/ASF, SC35, and SRp40 in exon 3 of Gαss. These results suggest that tissue-specific expression of SF2/ASF and hnRNPA1 governs the expression of alternative isoforms of Gαs in these different cells types.


Publication metadata

Author(s): Pollard AJ, Krainer AR, Robson SC, Europe-Finner GN

Publication type: Article

Publication status: Published

Journal: Journal of Biological Chemistry

Year: 2002

Volume: 277

Issue: 18

Pages: 15241-15251

ISSN (print): 0021-9258

ISSN (electronic): 1083-351X

Publisher: American Society for Biochemistry and Molecular Biology, Inc.

URL: http://dx.doi.org/10.1074/jbc.M109046200

DOI: 10.1074/jbc.M109046200

PubMed id: 11825891


Altmetrics

Altmetrics provided by Altmetric


Actions

    Link to this publication


Share