Abstract
The α-actinin gene has a pair of alternatively spliced exons. The smooth muscle (SM) exon is repressed in most cell types by polypyrimidine tract binding protein (PTB). CELF (CUG-BP and ETR3-like factors) family proteins, splicing regulators whose activities are altered in myotonic dystrophy, were found to coordinately regulate selection of the two α-actinin exons. CUG-BP and ETR3 activated the SM exon, and along with CELF4 they were also able to repress splicing of the NM (nonmuscle) exon both in vivo and in vitro. Activation of SM exon splicing was associated with displacement of PTB from the polypyrimidine tract by binding of CUG-BP at adjacent sites. Our data provides direct evidence for the activity of CELF proteins as both activators and repressors of splicing within a single-model system of alternative splicing, and suggests a model whereby α-actinin alternative splicing is regulated by synergistic and antagonistic interactions between members of the CELF and PTB families.
References
58
Referenced
84
10.1016/S0092-8674(00)00128-8
10.1016/S0968-0004(00)01549-8
- Burge, C., Tuschl, T., and Sharp, P. 1999. Splicing of precursors to mRNAs by the spliceosomes. In The RNA world, 2nd ed. (eds. R.F. Gestetland et al.), pp. 525â560. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
10.1016/S0168-9525(01)02626-9
10.1126/science.8085156
10.1093/emboj/18.14.4060
10.1038/nrg775
10.1016/S1097-2765(02)00479-3
10.1016/S1097-2765(02)00572-5
10.1016/S0378-1119(99)00312-1
10.1016/S1097-2765(00)80260-9
10.1128/MCB.18.8.4519
/ Mol. Cell. Biol. (1998)10.1128/MCB.19.1.251
/ Mol. Cell. Biol. (1999){'key': '2021112105331862000_9.4.443.14', 'first-page': '663', 'volume': '1', 'year': '1995', 'journal-title': 'RNA'}
/ RNA (1995)10.1074/jbc.M003083200
10.1002/j.1460-2075.1994.tb06697.x
/ EMBO J. (1994){'key': '2021112105331862000_9.4.443.17', 'first-page': '85', 'volume': '4', 'year': '1998', 'journal-title': 'RNA'}
/ RNA (1998)10.1017/S1355838200000960
10.1016/S0168-9525(00)02176-4
10.1093/nar/gkf480
10.1101/gad.13.4.437
/ Genes & Dev. (1999)10.1016/S0896-6273(00)80900-9
10.1016/S0955-0674(99)80051-9
10.1016/S0006-291X(02)00734-9
10.1128/MCB.21.4.1285-1296.2001
{'key': '2021112105331862000_9.4.443.26', 'first-page': '234', 'volume': '1', 'year': '1995', 'journal-title': 'RNA'}
/ RNA (1995)10.1146/annurev.genet.32.1.279
10.1093/hmg/8.1.53
10.1038/418236a
10.1016/S1097-2765(02)00563-4
10.1128/MCB.20.20.7463-7479.2000
-
McAfee, J.G., Huang, M., Soltaninassab, S., Rech, J.E., Iyengar, S., and Lesturgeon, W.M. 1997. The packaging of pre-mRNA. In Eukaryotic mRNA processing (ed. A.R. Krainer), pp. 68â102. Oxford University Press, Oxford/New York.
(
10.1093/oso/9780199634187.003.0003
) 10.1038/ng0102-13
-
Moore, M.J. and Query, C.C. 1998. Uses of site-specifically modified RNAs constructed by RNA ligation. In RNA protein interactions: A practical approach (ed. C.W.J. Smith), Vol. 192, pp. 75â108. Oxford University Press, Oxford.
(
10.1093/oso/9780199636518.003.0003
) {'key': '2021112105331862000_9.4.443.35', 'first-page': '764', 'volume': '3', 'year': '1997', 'journal-title': 'RNA'}
/ RNA (1997)10.1126/science.280.5364.737
10.1073/pnas.110128397
10.1016/S0955-0674(00)00097-1
10.1016/S1367-5931(02)00320-4
- Sambrook, J., Fritsch, E.F., and Maniatis, T. 1989. Molecular cloning: A laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
10.1038/ng704
10.1002/j.1460-2075.1995.tb07326.x
/ EMBO J. (1995)10.1126/science.7761834
10.1016/S0968-0004(00)01604-2
- Smith, C.W.J., Gooding, C., Roberts, G.C., and Scadden, A.D.J. 1996. Analyzing patterns of alternative splicing. In A laboratory guide to RNA. Isolation, analysis and synthesis (ed. P.A. Kreig), pp. 411â440. John Wiley & Sons, Inc., New York.
10.1128/MCB.19.4.2699
/ Mol. Cell. Biol. (1999)10.1046/j.1356-9597.2001.00506.x
10.1006/bbrc.2000.3694
10.1093/nar/24.22.4407
10.1093/hmg/5.1.115
10.1016/S0960-9822(06)00361-7
10.1128/MCB.21.10.3281-3288.2001
10.1016/S1097-2765(02)00645-7
10.1016/S0021-9258(18)42690-7
/ J. Biol. Chem. (1992)10.1017/S1355838201010214
10.1017/S1355838299981530
10.1017/S1355838202027036
10.1016/S1097-2765(01)00409-9
Dates
Type | When |
---|---|
Created | 22 years, 5 months ago (March 20, 2003, 5:44 p.m.) |
Deposited | 1 year, 7 months ago (Jan. 9, 2024, 9:16 a.m.) |
Indexed | 1 year ago (Aug. 10, 2024, 3:09 a.m.) |
Issued | 22 years, 5 months ago (April 1, 2003) |
Published | 22 years, 5 months ago (April 1, 2003) |
Published Online | 22 years, 5 months ago (April 1, 2003) |
Published Print | 22 years, 5 months ago (April 1, 2003) |
@article{GROMAK_2003, title={Antagonistic regulation of α-actinin alternative splicing by CELF proteins and polypyrimidine tract binding protein}, volume={9}, ISSN={1469-9001}, url={http://dx.doi.org/10.1261/rna.2191903}, DOI={10.1261/rna.2191903}, number={4}, journal={RNA}, publisher={Cold Spring Harbor Laboratory}, author={GROMAK, NATALIA and MATLIN, ARIANNE J. and COOPER, THOMAS A. and SMITH, CHRISTOPHER W.J.}, year={2003}, month=apr, pages={443–456} }