Author:
Lianoglou Steve,Garg Vidur,Yang Julie L.,Leslie Christina S.,Mayr Christine
Abstract
More than half of human genes use alternative cleavage and polyadenylation (ApA) to generate mRNA transcripts that differ in the lengths of their 3′ untranslated regions (UTRs), thus altering the post-transcriptional fate of the message and likely the protein output. The extent of 3′ UTR variation across tissues and the functional role of ApA remain poorly understood. We developed a sequencing method called 3′-seq to quantitatively map the 3′ ends of the transcriptome of diverse human tissues and isogenic transformation systems. We found that cell type-specific gene expression is accomplished by two complementary programs. Tissue-restricted genes tend to have single 3′ UTRs, whereas a majority of ubiquitously transcribed genes generate multiple 3′ UTRs. During transformation and differentiation, single-UTR genes change their mRNA abundance levels, while multi-UTR genes mostly change 3′ UTR isoform ratios to achieve tissue specificity. However, both regulation programs target genes that function in the same pathways and processes that characterize the new cell type. Instead of finding global shifts in 3′ UTR length during transformation and differentiation, we identify tissue-specific groups of multi-UTR genes that change their 3′ UTR ratios; these changes in 3′ UTR length are largely independent from changes in mRNA abundance. Finally, tissue-specific usage of ApA sites appears to be a mechanism for changing the landscape targetable by ubiquitously expressed microRNAs.
Publisher
Cold Spring Harbor Laboratory
Subject
Developmental Biology,Genetics
Cited by
328 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献