Alternative isoform regulation in human tissue transcriptomes Export

@article{citeulike:3474717, abstract = {Through alternative processing of pre-messenger RNAs, individual mammalian genes often produce multiple mRNA and protein isoforms that may have related, distinct or even opposing functions. Here we report an in-depth analysis of 15 diverse human tissue and cell line transcriptomes on the basis of deep sequencing of complementary DNA fragments, yielding a digital inventory of gene and mRNA isoform expression. Analyses in which sequence reads are mapped to exon–exon junctions indicated that 92–94\% of human genes undergo alternative splicing, 86\% with a minor isoform frequency of 15\% or more. Differences in isoform-specific read densities indicated that most alternative splicing and alternative cleavage and polyadenylation events vary between tissues, whereas variation between individuals was approximately twofold to threefold less common. Extreme or 'switch-like' regulation of splicing between tissues was associated with increased sequence conservation in regulatory regions and with generation of full-length open reading frames. Patterns of alternative splicing and alternative cleavage and polyadenylation were strongly correlated across tissues, suggesting coordinated regulation of these processes, and sequence conservation of a subset of known regulatory motifs in both alternative introns and 3' untranslated regions suggested common involvement of specific factors in tissue-level regulation of both splicing and polyadenylation.}, author = {Wang, Eric T. and Sandberg, Rickard and Luo, Shujun and Khrebtukova, Irina and Zhang, Lu and Mayr, Christine and Kingsmore, Stephen F. and Schroth, Gary P. and Burge, Christopher B.}, booktitle = {Nature}, citeulike-article-id = {3474717}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nature07509}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/nature07509}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18978772}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18978772}, day = {02}, doi = {10.1038/nature07509}, issn = {0028-0836}, journal = {Nature}, keywords = {alternative, deep-seq, human, rna, rna-seq, splicing, transcription}, month = {November}, number = {7221}, pages = {470--476}, posted-at = {2008-11-05 09:41:21}, priority = {2}, publisher = {Nature Publishing Group}, title = {Alternative isoform regulation in human tissue transcriptomes}, url = {http://dx.doi.org/10.1038/nature07509}, volume = {456}, year = {2008} }

TY - JOUR ID - citeulike:3474717 L3 - citeulike-article-id:3474717 N2 - Through alternative processing of pre-messenger RNAs, individual mammalian genes often produce multiple mRNA and protein isoforms that may have related, distinct or even opposing functions. Here we report an in-depth analysis of 15 diverse human tissue and cell line transcriptomes on the basis of deep sequencing of complementary DNA fragments, yielding a digital inventory of gene and mRNA isoform expression. Analyses in which sequence reads are mapped to exon–exon junctions indicated that 92–94% of human genes undergo alternative splicing, 86% with a minor isoform frequency of 15% or more. Differences in isoform-specific read densities indicated that most alternative splicing and alternative cleavage and polyadenylation events vary between tissues, whereas variation between individuals was approximately twofold to threefold less common. Extreme or 'switch-like' regulation of splicing between tissues was associated with increased sequence conservation in regulatory regions and with generation of full-length open reading frames. Patterns of alternative splicing and alternative cleavage and polyadenylation were strongly correlated across tissues, suggesting coordinated regulation of these processes, and sequence conservation of a subset of known regulatory motifs in both alternative introns and 3' untranslated regions suggested common involvement of specific factors in tissue-level regulation of both splicing and polyadenylation. IS - 7221 JF - Nature SN - 0028-0836 EP - 476 TI - Alternative isoform regulation in human tissue transcriptomes PB - Nature Publishing Group VL - 456 T2 - Nature SP - 470 KW - alternative KW - deep-seq KW - human KW - rna KW - rna-seq KW - splicing KW - transcription AU - Wang, Eric AU - Sandberg, Rickard AU - Luo, Shujun AU - Khrebtukova, Irina AU - Zhang, Lu AU - Mayr, Christine AU - Kingsmore, Stephen AU - Schroth, Gary AU - Burge, Christopher PY - 2008/11/02/ UR - http://dx.doi.org/10.1038/nature07509 ER -