NDLI: Subcellular RNA profiling links splicing and nuclear DICER1 to alternative cleavage and polyadenylation.

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Subcellular RNA profiling links splicing and nuclear DICER1 to alternative cleavage and polyadenylation.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Neve, Jonathan Burger, Kaspar Li, Wencheng Hoque, Mainul Patel, Radhika Tian, Bin Gullerova, Monika Furger, Andre
Description	Author Affiliation: Neve J ( Department of Biochemistry, University of Oxford, OX1 3QU, United Kingdom); Burger K ( Sir William Dunn School of Pathology, University of Oxford, OX1 3RE, United Kingdom); Li W ( Department of Biochemistry and Molecular Biology, Rutgers New Jersey Medical School, Newark, New Jersey 07103, USA.); Hoque M ( Department of Biochemistry and Molecular Biology, Rutgers New Jersey Medical School, Newark, New Jersey 07103, USA.); Patel R ( Department of Biochemistry, University of Oxford, OX1 3QU, United Kingdom); Tian B ( Department of Biochemistry and Molecular Biology, Rutgers New Jersey Medical School, Newark, New Jersey 07103, USA.); Gullerova M ( Sir William Dunn School of Pathology, University of Oxford, OX1 3RE, United Kingdom); Furger A ( Department of Biochemistry, University of Oxford, OX1 3QU, United Kingdom)
Abstract	Alternative cleavage and polyadenylation (APA) plays a crucial role in the regulation of gene expression across eukaryotes. Although APA is extensively studied, its regulation within cellular compartments and its physiological impact remains largely enigmatic. Here, we used a rigorous subcellular fractionation approach to compare APA profiles of cytoplasmic and nuclear RNA fractions from human cell lines. This approach allowed us to extract APA isoforms that are subjected to differential regulation and provided us with a platform to interrogate the molecular regulatory pathways that shape APA profiles in different subcellular locations. Here, we show that APA isoforms with shorter 3' UTRs tend to be overrepresented in the cytoplasm and appear to be cell-type-specific events. Nuclear retention of longer APA isoforms occurs and is partly a result of incomplete splicing contributing to the observed cytoplasmic bias of transcripts with shorter 3' UTRs. We demonstrate that the endoribonuclease III, DICER1, contributes to the establishment of subcellular APA profiles not only by expected cytoplasmic miRNA-mediated destabilization of APA mRNA isoforms, but also by affecting polyadenylation site choice.
File Format	HTM / HTML
ISSN	10889051
e-ISSN	15495469
DOI	10.1101/gr.193995.115
Journal	Genome Research
Issue Number	1
Volume Number	26
Language	English
Publisher	Cold Spring Harbor Laboratory Press
Publisher Date	2016-01-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Genetics Discipline Genomics Dead-box Rna Helicases Genetics Gene Expression Profiling Polyadenylation Rna Splicing Ribonuclease Iii 3' Untranslated Regions Metabolism Gene Expression Regulation Genome, Human Hek293 Cells High-throughput Nucleotide Sequencing Metallochaperones Micrornas Protein Isoforms Rna Stability Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Genetics Genetics (clinical)

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Subcellular RNA profiling links splicing and nuclear DICER1 to alternative cleavage and polyadenylation

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Subcellular RNA profiling links splicing and nuclear DICER1 to alternative cleavage and polyadenylation.

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