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Báo cáo khoa học: Alternative splicing: global insights

Following the original reports of pre-mRNA splicing in 1977, it was quickly realized that splicing together of different combinations of splice sites – alternative splicing– allows individual genes to generate more than one mRNA isoform. The full extent of alternative splicing only began to be revealed once large-scale genome and transcriptome sequencing projects began, rapidly revealing that alternative splicing is the rule rather than the exception. | MINIREVIEW Alternative splicing global insights Martina Hallegger Miriam Llorian and Christopher W. J. Smith Department of Biochemistry University of Cambridge UK Keywords alternative splicing microarray RNA-Seq Correspondence C. W. J. Smith Department of Biochemistry University of Cambridge 80 Tennis Court Road Cambridge CB2 1GA UK Fax 44 1223 766002 Tel 44 1223 333655 E-mail cwjs1@cam.ac.uk These authors contributed equally to this work Received 26 August 2009 accepted 22 October 2009 Following the original reports of pre-mRNA splicing in 1977 it was quickly realized that splicing together of different combinations of splice sites - alternative splicing- allows individual genes to generate more than one mRNA isoform. The full extent of alternative splicing only began to be revealed once large-scale genome and transcriptome sequencing projects began rapidly revealing that alternative splicing is the rule rather than the exception. Recent technical innovations have facilitated the investigation of alternative splicing at a global scale. Splice-sensitive microarray platforms and deep sequencing allow quantitative profiling of very large numbers of alternative splicing events whereas global analysis of the targets of RNA binding proteins reveals the regulatory networks involved in post-transcriptional gene control. Combined with sophisticated computational analysis these new approaches are beginning to reveal the so-called RNA code that underlies tissue and developmentally regulated alternative splicing and that can be disrupted by disease-causing mutations. doi 10.1111 j.1742-4658.2009.07521.x Introduction Alternative splicing allows individual genes to produce two or more variant mRNAs which in many cases encode functionally distinct proteins. With the progressive generation of ever larger sequence datasets the proportion of multi-exon human genes that are known to be alternatively spliced has expanded to 92-94 of which 85 have a minor isoform frequency of at least