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Alternative isoform regulation in human tissue transcriptomes.

来自 EBSCO

阅读量：

1148

作者：

ET Wang，R Sandberg，S Luo，I Khrebtukova，L Zhang，C Mayr，SF Kingsmore，GP Schroth，CB Burge

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摘要：

Through alternative processing of pre-mRNAs, 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 based on deep sequencing of cDNA fragments, yielding a digital inventory of gene and mRNA isoform expression. Analysis of mappings of sequence reads to exon-exon junctions indicated that 92-94% of human genes undergo alternative splicing (AS), 86% with a minor isoform frequency of 15% or more. Differences in isoform-specific read densities indicated that a majority of AS and of alternative cleavage and polyadenylation (APA) events vary between tissues, while variation between individuals was 2- to 3-fold 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 AS and APA 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′ UTRs suggested common involvement of specific factors in tissue-level regulation of both splicing and polyadenylation.

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关键词：

Humans Cell Line Repressor Proteins RNA-Binding Proteins Gene Expression Profiling Base Sequence Exons Organ Specificity Polyadenylation Alternative Splicing

DOI：

10.1038/nature07509

被引量：

6664

年份：

2008

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