Ubiquitously transcribed genes use alternative polyadenylation to achieve tissue-specific expression
TLDR
This work developed a sequencing method called 3'-seq to quantitatively map the 3' ends of the transcriptome of diverse human tissues and isogenic transformation systems and found that cell type-specific gene expression is accomplished by two complementary programs.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.read more
Citations
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Widespread intronic polyadenylation inactivates tumour suppressor genes in leukaemia.
Shih-Han Lee,Irtisha Singh,Sarah Tisdale,Omar Abdel-Wahab,Christina S. Leslie,Christine Mayr +5 more
TL;DR: Findings show the need to go beyond genomic analyses in cancer diagnostics, as mRNA events that are silent at the DNA level are widespread contributors to cancer pathogenesis through the inactivation of tumour-suppressor genes.
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PolyA_DB 3 catalogs cleavage and polyadenylation sites identified by deep sequencing in multiple genomes.
TL;DR: An updated version of the database cataloging cleavage and polyadenylation sites (PASs) in several genomes based solely on deep sequencing data is presented, ensuring unequivocal PAS identification.
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Alternative mRNA splicing in cancer immunotherapy
TL;DR: The promise of analysing mRNA processing events in cancer cells, with an emphasis on mRNA splicing, for the identification of potential new targets for cancer immunotherapy is discussed.
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Fip1 regulates mRNA alternative polyadenylation to promote stem cell self-renewal
Brad Lackford,Chengguo Yao,Georgette M. Charles,Lingjie Weng,Xiaofeng Zheng,Eun-A Choi,Xiaohui Xie,Ji Wan,Yi Xing,Yi Xing,Johannes M. Freudenberg,Pengyi Yang,Raja Jothi,Guang Hu,Yongsheng Shi +14 more
TL;DR: It is shown that an mRNA 3′ processing factor, Fip1, is essential for embryonic stem cell self‐renewal and somatic cell reprogramming and mechanistic insight is provided on APA regulation in development and an important function for APA in cell fate specification is established.
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QAPA: a new method for the systematic analysis of alternative polyadenylation from RNA-seq data
TL;DR: Application of QAPA reveals discrete, temporally coordinated APA programs during neurogenesis and that there is little overlap between genes regulated by alternative splicing and those by APA.
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