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...
Main Authors: | , , , , , , , |
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Format: | Article |
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eLife Sciences Publications Ltd
2018-03-01
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Series: | eLife |
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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. |
first_indexed | 2024-04-12T12:15:17Z |
format | Article |
id | doaj.art-0eab42023df64bc289ab7e10fb10d84f |
institution | Directory Open Access Journal |
issn | 2050-084X |
language | English |
last_indexed | 2024-04-12T12:15:17Z |
publishDate | 2018-03-01 |
publisher | eLife Sciences Publications Ltd |
record_format | Article |
series | eLife |
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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