Tags

Type your tag names separated by a space and hit enter

Regulation of alternative splicing by PTB and associated factors.
Biochem Soc Trans. 2005 Jun; 33(Pt 3):457-60.BS

Abstract

PTB (polypyrimidine tract-binding protein) is a repressive regulator of alternative splicing. We have investigated the role of PTB in three model alternative splicing systems. In the alpha-actinin gene, PTB represses the SM (smooth muscle) exon by binding to key sites in the polypyrimidine tract. Repressive binding to these sites is assisted by co-operative binding to additional downstream sites. SM exon splicing can be activated by CELF proteins, which also bind co-operatively to interspersed sites and displace PTB from the pyrimidine tract. Exon 11 of PTB pre-mRNA is repressed by PTB in an autoregulatory feedback loop. Exon 11-skipped RNA gets degraded through nonsense-mediated decay. Less than 1% of steady-state PTB mRNA is represented by this isoform, but inhibition of nonsense-mediated decay by RNA interference against Upf1 shows that at least 20% of PTB RNA is consumed by this pathway. This represents a widespread but under-appreciated role of alternative splicing in the quantitative regulation of gene expression, an important addition to its role as a generator of protein isoform diversity. Repression of alpha-tropomyosin exon 3 is an exceptional example of PTB regulation, because repression only occurs at high levels in SM cells, despite the fact that PTB is widely expressed. In this case, a PTB-interacting cofactor, raver1, appears to play an important role. By the use of 'tethering' assays, we have identified discrete domains within both PTB and raver1 that mediate their repressive activities on this splicing event.

Authors+Show Affiliations

Department of Biochemistry, University of Cambridge, 80, Tennis Court Road, Cambridge CB2 1GA, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

15916540

Citation

Spellman, R, et al. "Regulation of Alternative Splicing By PTB and Associated Factors." Biochemical Society Transactions, vol. 33, no. Pt 3, 2005, pp. 457-60.
Spellman R, Rideau A, Matlin A, et al. Regulation of alternative splicing by PTB and associated factors. Biochem Soc Trans. 2005;33(Pt 3):457-60.
Spellman, R., Rideau, A., Matlin, A., Gooding, C., Robinson, F., McGlincy, N., Grellscheid, S. N., Southby, J., Wollerton, M., & Smith, C. W. (2005). Regulation of alternative splicing by PTB and associated factors. Biochemical Society Transactions, 33(Pt 3), 457-60.
Spellman R, et al. Regulation of Alternative Splicing By PTB and Associated Factors. Biochem Soc Trans. 2005;33(Pt 3):457-60. PubMed PMID: 15916540.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of alternative splicing by PTB and associated factors. AU - Spellman,R, AU - Rideau,A, AU - Matlin,A, AU - Gooding,C, AU - Robinson,F, AU - McGlincy,N, AU - Grellscheid,S N, AU - Southby,J, AU - Wollerton,M, AU - Smith,C W J, PY - 2005/5/27/pubmed PY - 2005/8/17/medline PY - 2005/5/27/entrez SP - 457 EP - 60 JF - Biochemical Society transactions JO - Biochem Soc Trans VL - 33 IS - Pt 3 N2 - PTB (polypyrimidine tract-binding protein) is a repressive regulator of alternative splicing. We have investigated the role of PTB in three model alternative splicing systems. In the alpha-actinin gene, PTB represses the SM (smooth muscle) exon by binding to key sites in the polypyrimidine tract. Repressive binding to these sites is assisted by co-operative binding to additional downstream sites. SM exon splicing can be activated by CELF proteins, which also bind co-operatively to interspersed sites and displace PTB from the pyrimidine tract. Exon 11 of PTB pre-mRNA is repressed by PTB in an autoregulatory feedback loop. Exon 11-skipped RNA gets degraded through nonsense-mediated decay. Less than 1% of steady-state PTB mRNA is represented by this isoform, but inhibition of nonsense-mediated decay by RNA interference against Upf1 shows that at least 20% of PTB RNA is consumed by this pathway. This represents a widespread but under-appreciated role of alternative splicing in the quantitative regulation of gene expression, an important addition to its role as a generator of protein isoform diversity. Repression of alpha-tropomyosin exon 3 is an exceptional example of PTB regulation, because repression only occurs at high levels in SM cells, despite the fact that PTB is widely expressed. In this case, a PTB-interacting cofactor, raver1, appears to play an important role. By the use of 'tethering' assays, we have identified discrete domains within both PTB and raver1 that mediate their repressive activities on this splicing event. SN - 0300-5127 UR - https://www.unboundmedicine.com/medline/citation/15916540/Regulation_of_alternative_splicing_by_PTB_and_associated_factors_ L2 - https://portlandpress.com/biochemsoctrans/article-lookup/doi/10.1042/BST0330457 DB - PRIME DP - Unbound Medicine ER -