Differential 3’ processing of specific transcripts expands regulatory and protein diversity across neuronal cell types

Alternative polyadenylation (APA) regulates mRNA translation, stability, and protein localization. However, it is unclear to what extent APA regulates these processes uniquely in specific cell types. Using a new technique, cTag-PAPERCLIP, we discovered significant differences in APA between the prin...

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Main Authors: Saša Jereb, Hun-Way Hwang, Eric Van Otterloo, Eve-Ellen Govek, John J Fak, Yuan Yuan, Mary E Hatten, Robert B Darnell
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2018-03-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/34042
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author Saša Jereb
Hun-Way Hwang
Eric Van Otterloo
Eve-Ellen Govek
John J Fak
Yuan Yuan
Mary E Hatten
Robert B Darnell
author_facet Saša Jereb
Hun-Way Hwang
Eric Van Otterloo
Eve-Ellen Govek
John J Fak
Yuan Yuan
Mary E Hatten
Robert B Darnell
author_sort Saša Jereb
collection DOAJ
description Alternative polyadenylation (APA) regulates mRNA translation, stability, and protein localization. However, it is unclear to what extent APA regulates these processes uniquely in specific cell types. Using a new technique, cTag-PAPERCLIP, we discovered significant differences in APA between the principal types of mouse cerebellar neurons, the Purkinje and granule cells, as well as between proliferating and differentiated granule cells. Transcripts that differed in APA in these comparisons were enriched in key neuronal functions and many differed in coding sequence in addition to 3’UTR length. We characterize Memo1, a transcript that shifted from expressing a short 3’UTR isoform to a longer one during granule cell differentiation. We show that Memo1 regulates granule cell precursor proliferation and that its long 3’UTR isoform is targeted by miR-124, contributing to its downregulation during development. Our findings provide insight into roles for APA in specific cell types and establish a platform for further functional studies.
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spelling doaj.art-0eab42023df64bc289ab7e10fb10d84f2022-12-22T03:33:26ZengeLife Sciences Publications LtdeLife2050-084X2018-03-01710.7554/eLife.34042Differential 3’ processing of specific transcripts expands regulatory and protein diversity across neuronal cell typesSaša Jereb0https://orcid.org/0000-0001-6862-4475Hun-Way Hwang1Eric Van Otterloo2Eve-Ellen Govek3John J Fak4Yuan Yuan5https://orcid.org/0000-0002-2718-8301Mary E Hatten6https://orcid.org/0000-0001-9059-660XRobert B Darnell7https://orcid.org/0000-0002-5134-8088Laboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute, The Rockefeller University, New York, United StatesLaboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute, The Rockefeller University, New York, United StatesDepartment of Craniofacial Biology, University of Colorado Anschutz Medical Campus, Aurora, United StatesLaboratory of Developmental Neurobiology, The Rockefeller University, New York, United StatesLaboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute, The Rockefeller University, New York, United StatesLaboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute, The Rockefeller University, New York, United StatesLaboratory of Developmental Neurobiology, The Rockefeller University, New York, United StatesLaboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute, The Rockefeller University, New York, United StatesAlternative polyadenylation (APA) regulates mRNA translation, stability, and protein localization. However, it is unclear to what extent APA regulates these processes uniquely in specific cell types. Using a new technique, cTag-PAPERCLIP, we discovered significant differences in APA between the principal types of mouse cerebellar neurons, the Purkinje and granule cells, as well as between proliferating and differentiated granule cells. Transcripts that differed in APA in these comparisons were enriched in key neuronal functions and many differed in coding sequence in addition to 3’UTR length. We characterize Memo1, a transcript that shifted from expressing a short 3’UTR isoform to a longer one during granule cell differentiation. We show that Memo1 regulates granule cell precursor proliferation and that its long 3’UTR isoform is targeted by miR-124, contributing to its downregulation during development. Our findings provide insight into roles for APA in specific cell types and establish a platform for further functional studies.https://elifesciences.org/articles/34042alternative polyadenylationcerebellumPurkinje cellsgranule cells
spellingShingle Saša Jereb
Hun-Way Hwang
Eric Van Otterloo
Eve-Ellen Govek
John J Fak
Yuan Yuan
Mary E Hatten
Robert B Darnell
Differential 3’ processing of specific transcripts expands regulatory and protein diversity across neuronal cell types
eLife
alternative polyadenylation
cerebellum
Purkinje cells
granule cells
title Differential 3’ processing of specific transcripts expands regulatory and protein diversity across neuronal cell types
title_full Differential 3’ processing of specific transcripts expands regulatory and protein diversity across neuronal cell types
title_fullStr Differential 3’ processing of specific transcripts expands regulatory and protein diversity across neuronal cell types
title_full_unstemmed Differential 3’ processing of specific transcripts expands regulatory and protein diversity across neuronal cell types
title_short Differential 3’ processing of specific transcripts expands regulatory and protein diversity across neuronal cell types
title_sort differential 3 processing of specific transcripts expands regulatory and protein diversity across neuronal cell types
topic alternative polyadenylation
cerebellum
Purkinje cells
granule cells
url https://elifesciences.org/articles/34042
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AT hunwayhwang differential3processingofspecifictranscriptsexpandsregulatoryandproteindiversityacrossneuronalcelltypes
AT ericvanotterloo differential3processingofspecifictranscriptsexpandsregulatoryandproteindiversityacrossneuronalcelltypes
AT eveellengovek differential3processingofspecifictranscriptsexpandsregulatoryandproteindiversityacrossneuronalcelltypes
AT johnjfak differential3processingofspecifictranscriptsexpandsregulatoryandproteindiversityacrossneuronalcelltypes
AT yuanyuan differential3processingofspecifictranscriptsexpandsregulatoryandproteindiversityacrossneuronalcelltypes
AT maryehatten differential3processingofspecifictranscriptsexpandsregulatoryandproteindiversityacrossneuronalcelltypes
AT robertbdarnell differential3processingofspecifictranscriptsexpandsregulatoryandproteindiversityacrossneuronalcelltypes