The architecture of pre-mRNAs affects mechanisms of splice-site pairing Export

@article{citeulike:399693, abstract = {10.1073/pnas.0508489102 The exon/intron architecture of genes determines whether components of the spliceosome recognize splice sites across the intron or across the exon. Using splicing assays, we demonstrate that splice-site recognition across introns ceases when intron size is between 200 and 250 nucleotides. Beyond this threshold, splice sites are recognized across the exon. Splice-site recognition across the intron is significantly more efficient than splice-site recognition across the exon, resulting in enhanced inclusion of exons with weak splice sites. Thus, intron size can profoundly influence the likelihood that an exon is constitutively or alternatively spliced. An EST-based alternative-splicing database was used to determine whether the exon/intron architecture influences the probability of alternative splicing in the and human genomes. exons flanked by long introns display an up to 90-fold-higher probability of being alternatively spliced compared with exons flanked by two short introns, demonstrating that the exon/intron architecture in is a major determinant in governing the frequency of alternative splicing. Exon skipping is also more likely to occur when exons are flanked by long introns in the human genome. Interestingly, experimental and computational analyses show that the length of the upstream intron is more influential in inducing alternative splicing than is the length of the downstream intron. We conclude that the size and location of the flanking introns control the mechanism of splice-site recognition and influence the frequency and the type of alternative splicing that a pre-mRNA transcript undergoes.}, address = {Departments of Microbiology and Molecular Genetics and Information and Computer Sciences, University of California, Irvine, CA 92697-4025.}, author = {Fox-Walsh, Kristi L. and Dou, Yimeng and Lam, Bianca J. and Hung, She-pin and Baldi, Pierre F. and Hertel, Klemens J.}, citeulike-article-id = {399693}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0508489102}, citeulike-linkout-1 = {http://www.pnas.org/content/102/45/16176.abstract}, citeulike-linkout-2 = {http://www.pnas.org/content/102/45/16176.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/16260721}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=16260721}, day = {8}, doi = {10.1073/pnas.0508489102}, issn = {0027-8424}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, keywords = {intron, length}, month = {November}, number = {45}, pages = {16176--16181}, posted-at = {2009-11-02 15:19:39}, priority = {2}, title = {The architecture of pre-mRNAs affects mechanisms of splice-site pairing}, url = {http://dx.doi.org/10.1073/pnas.0508489102}, volume = {102}, year = {2005} }

TY - JOUR ID - citeulike:399693 L3 - citeulike-article-id:399693 N2 - 10.1073/pnas.0508489102 The exon/intron architecture of genes determines whether components of the spliceosome recognize splice sites across the intron or across the exon. Using splicing assays, we demonstrate that splice-site recognition across introns ceases when intron size is between 200 and 250 nucleotides. Beyond this threshold, splice sites are recognized across the exon. Splice-site recognition across the intron is significantly more efficient than splice-site recognition across the exon, resulting in enhanced inclusion of exons with weak splice sites. Thus, intron size can profoundly influence the likelihood that an exon is constitutively or alternatively spliced. An EST-based alternative-splicing database was used to determine whether the exon/intron architecture influences the probability of alternative splicing in the and human genomes. exons flanked by long introns display an up to 90-fold-higher probability of being alternatively spliced compared with exons flanked by two short introns, demonstrating that the exon/intron architecture in is a major determinant in governing the frequency of alternative splicing. Exon skipping is also more likely to occur when exons are flanked by long introns in the human genome. Interestingly, experimental and computational analyses show that the length of the upstream intron is more influential in inducing alternative splicing than is the length of the downstream intron. We conclude that the size and location of the flanking introns control the mechanism of splice-site recognition and influence the frequency and the type of alternative splicing that a pre-mRNA transcript undergoes. IS - 45 JF - Proceedings of the National Academy of Sciences of the United States of America SN - 0027-8424 AD - Departments of Microbiology and Molecular Genetics and Information and Computer Sciences, University of California, Irvine, CA 92697-4025. EP - 16181 TI - The architecture of pre-mRNAs affects mechanisms of splice-site pairing VL - 102 SP - 16176 KW - intron KW - length AU - Fox-Walsh, Kristi AU - Dou, Yimeng AU - Lam, Bianca AU - Hung, She-pin AU - Baldi, Pierre AU - Hertel, Klemens PY - 2005/11/08/ UR - http://dx.doi.org/10.1073/pnas.0508489102 ER -