Nucleic Acids Research, 2001, Vol. 29, No. 12 2581-2593
© 2001 Oxford University Press
Human GC-AG alternative intron isoforms with weak donor sites show enhanced consensus at acceptor exon positions
European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK and 1University of Queensland, St Lucia, 4072, Australia
It has been previously observed that the intrinsically weak variant GC donor sites, in order to be recognized by the U2-type spliceosome, possess strong consensus sequences maximized for base pair formation with U1 and U5/U6 snRNAs. However, variability in signal strength is a fundamental mechanism for splice site selection in alternative splicing. Here we report human alternative GC-AG introns (for the first time from any species), and show that while constitutive GC-AG introns do possess strong signals at their donor sites, a large subset of alternative GC-AG introns possess weak consensus sequences at their donor sites. Surprisingly, this subset of alternative isoforms shows strong consensus at acceptor exon positions 1 and 2. The improved consensus at the acceptor exon can facilitate a strong interaction with U5 snRNA, which tethers the two exons for ligation during the second step of splicing. Further, these isoforms nearly always possess alternative acceptor sites and exhibit particularly weak polypyrimidine tracts characteristic of AG-dependent introns. The acceptor exon nucleotides are part of the consensus required for the U2AF35-mediated recognition of AG in such introns. Such improved consensus at acceptor exons is not found in either normal or alternative GT-AG introns having weak donor sites or weak polypyrimidine tracts. The changes probably reflect mechanisms that allow GC-AG alternative intron isoforms to cope with two conflicting requirements, namely an apparent need for differential splice strength to direct the choice of alternative sites and a need for improved donor signals to compensate for the central mismatch base pair (C-A) in the RNA duplex of U1 snRNA and the pre-mRNA. The other important findings include (i) one in every twenty alternative introns is a GC-AG intron, and (ii) three of every five observed GC-AG introns are alternative isoforms.
* To whom correspondence should be addressed. Tel: +44 1223 494650; Fax: +44 1223 494468; Email: thanaraj{at}ebi.ac.uk
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. D. Wilkerson, Y. Ru, and V. P. Brendel Common introns within orthologous genes: software and application to plants Brief Bioinform, November 1, 2009; 10(6): 631 - 644. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Graham, S. A. F. Jegouzo, S. Yan, A. S. Powlesland, J. P. Brady, M. E. Taylor, and K. Drickamer Prolectin, a Glycan-binding Receptor on Dividing B Cells in Germinal Centers J. Biol. Chem., July 3, 2009; 284(27): 18537 - 18544. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E.-Y. Choi and D. Pintel Splicing of the Large Intron Present in the Nonstructural Gene of Minute Virus of Mice Is Governed by TIA-1/TIAR Binding Downstream of the Nonconsensus Donor J. Virol., June 15, 2009; 83(12): 6306 - 6311. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Mandal, Z. Feng, and C. M. Stoltzfus Gag-Processing Defect of Human Immunodeficiency Virus Type 1 Integrase E246 and G247 Mutants Is Caused by Activation of an Overlapping 5' Splice Site J. Virol., February 1, 2008; 82(3): 1600 - 1604. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Tachu, S. Pillai, R. Lucius, and T. Pogonka Essential Role of Chitinase in the Development of the Filarial Nematode Acanthocheilonema viteae Infect. Immun., January 1, 2008; 76(1): 221 - 228. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Lykke-Andersen, S. Pinol-Roma, and J. Kjems Alternative splicing of the ADAR1 transcript in a region that functions either as a 5'-UTR or an ORF RNA, October 1, 2007; 13(10): 1732 - 1744. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L D. Valle, V Toffolo, A Nardi, C Fiore, P Bernante, R Di Liddo, P. Parnigotto, and L Colombo Tissue-specific transcriptional initiation and activity of steroid sulfatase complementing dehydroepiandrosterone sulfate uptake and intracrine steroid activations in human adipose tissue. J. Endocrinol., July 1, 2006; 190(1): 129 - 139. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Barak, M. A. Lazzaro, N. S. Cooch, D. J. Picketts, and R. Shiekhattar A Tissue-specific, Naturally Occurring Human SNF2L Variant Inactivates Chromatin Remodeling J. Biol. Chem., October 22, 2004; 279(43): 45130 - 45138. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. Devor and K. Moffat-Wilson An Ancient RNase H1 Splice Junction Mutant Preserved in a 19-Million-Year-Old Genetic Fossil in Ape Genomes J. Hered., May 1, 2004; 95(3): 257 - 261. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Borgono, I. P. Michael, and E. P. Diamandis Human Tissue Kallikreins: Physiologic Roles and Applications in Cancer Mol. Cancer Res., May 1, 2004; 2(5): 257 - 280. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Eden and S. Brunak Analysis and recognition of 5' UTR intron splice sites in human pre-mRNA Nucleic Acids Res., February 11, 2004; 32(3): 1131 - 1142. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Jin, J. Zhang, C. Rowe-Teeter, J. Yang, L. L. Stuve, and G. K. Fu Cloning and Characterization of a GABAA Receptor {gamma}2 Subunit Variant J. Biol. Chem., January 9, 2004; 279(2): 1408 - 1414. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. Thanaraj, S. Stamm, F. Clark, J.-J. Riethoven, V. Le Texier, and J. Muilu ASD: the Alternative Splicing Database Nucleic Acids Res., January 1, 2004; 32(90001): D64 - 69. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Hogan, M. D. Griffin, S. Rossetti, V. E. Torres, C. J. Ward, and P. C. Harris PKHDL1, a homolog of the autosomal recessive polycystic kidney disease gene, encodes a receptor with inducible T lymphocyte expression Hum. Mol. Genet., March 15, 2003; 12(6): 685 - 698. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R. Wilund, M. Yi, F. Campagna, M. Arca, G. Zuliani, R. Fellin, Y.-K. Ho, J. V. Garcia, H. H. Hobbs, and J. C. Cohen Molecular mechanisms of autosomal recessive hypercholesterolemia Hum. Mol. Genet., November 15, 2002; 11(24): 3019 - 3030. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Farrer, A. B. Roller, W. J. Kent, and A. M. Zahler Analysis of the role of Caenorhabditis elegans GC-AG introns in regulated splicing Nucleic Acids Res., August 1, 2002; 30(15): 3360 - 3367. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Clark and T. A. Thanaraj Categorization and characterization of transcript-confirmed constitutively and alternatively spliced introns and exons from human Hum. Mol. Genet., February 1, 2002; 11(4): 451 - 464. [Abstract] [Full Text] [PDF]
|
|