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
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References
More filters
Journal ArticleDOI
MicroRNAs: Genomics, Biogenesis, Mechanism, and Function
TL;DR: Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.
Journal ArticleDOI
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources.
TL;DR: By following this protocol, investigators are able to gain an in-depth understanding of the biological themes in lists of genes that are enriched in genome-scale studies.
Journal ArticleDOI
Differential expression analysis for sequence count data.
Simon Anders,Wolfgang Huber +1 more
TL;DR: A method based on the negative binomial distribution, with variance and mean linked by local regression, is proposed and an implementation, DESeq, as an R/Bioconductor package is presented.
Journal ArticleDOI
MicroRNA expression profiles classify human cancers
Jun Lu,Gad Getz,Eric A. Miska,Eric A. Miska,Ezequiel Alvarez-Saavedra,Justin Lamb,David Peck,Alejandro Sweet-Cordero,Alejandro Sweet-Cordero,Benjamin L. Ebert,Benjamin L. Ebert,Raymond H. Mak,Raymond H. Mak,Adolfo A. Ferrando,James R. Downing,Tyler Jacks,H. Robert Horvitz,H. Robert Horvitz,Todd R. Golub,Todd R. Golub,Todd R. Golub +20 more
TL;DR: A new, bead-based flow cytometric miRNA expression profiling method is used to present a systematic expression analysis of 217 mammalian miRNAs from 334 samples, including multiple human cancers, and finds the miRNA profiles are surprisingly informative, reflecting the developmental lineage and differentiation state of the tumours.
Journal ArticleDOI
A mammalian microRNA expression atlas based on small RNA library sequencing.
Pablo Landgraf,Mirabela Rusu,Robert L. Sheridan,Alain Sewer,Alain Sewer,Nicola Iovino,Alexei A. Aravin,Sébastien Pfeffer,Amanda J. Rice,Alice O. Kamphorst,Markus Landthaler,Carolina Lin,Nicholas D. Socci,Leandro C. Hermida,Valerio Fulci,Sabina Chiaretti,Robin Foà,Julia Schliwka,Uta Fuchs,Astrid Novosel,Roman-Ulrich Müller,Roman-Ulrich Müller,Bernhard Schermer,Ute Bissels,Jason M. Inman,Quang Phan,Minchen Chien,David B. Weir,Ruchi Choksi,Gabriella De Vita,Daniela Frezzetti,Hans Ingo Trompeter,Veit Hornung,Grace Teng,Gunther Hartmann,Miklós Palkovits,Roberto Di Lauro,Peter Wernet,Giuseppe Macino,Charles E. Rogler,James W. Nagle,Jingyue Ju,F. Nina Papavasiliou,Thomas Benzing,Peter Lichter,Wayne Tam,Michael J. Brownstein,Andreas Bosio,Arndt Borkhardt,James J. Russo,Chris Sander,Mihaela Zavolan,Mihaela Zavolan,Thomas Tuschl +53 more
TL;DR: A relatively small set of miRNAs, many of which are ubiquitously expressed, account for most of the differences in miRNA profiles between cell lineages and tissues.
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