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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Transcriptome sequencing suggests that pre-mRNA splicing counteracts widespread intronic cleavage and polyadenylation
TL;DR: In this article , a combination of computational methods including the analysis of short reads with non-templated adenines revealed that APA events are more abundant in introns than in exons.
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Alternative polyadenylation factor CPSF6 regulates temperature compensation of the mammalian circadian clock
Christoph Schmal,Bert Maier,Reut Ashwal-Fluss,Osnat Bartok,Anna-Marie Finger,Stella Koutsouli,Maria S. Robles,Sebastian Kadener,Hanspeter Herzel,Achim Kramer +9 more
TL;DR: In this article , a combination of 3′-end-RNA-seq and mass spectrometry-based proteomics was applied to globally quantify changes in 3′ UTR length as well as gene and protein expression between wild-type and CPSF6 knockdown cells and their dependency on temperature.
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The landscape of alternative polyadenylation during EMT and its regulation by the RNA-binding protein Quaking
Daniel P. Neumann,Katherine A. Pillman,B. Kate Dredge,Andrew G. Bert,Cameron P. Bracken,Brett G. Hollier,Luke A. Selth,Traude H. Beilharz,Gregory J. Goodall,Philip A. Gregory +9 more
TL;DR: In this article , the authors explored the extent of alternative polyadenylation (APA) during EMT using 3' end anchored RNA sequencing, and found APA generally causes 3'UTR lengthening during this cell state transition.
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