Differential 3' processing of specific transcripts expands regulatory and protein diversity across neuronal cell types
- The Rockefeller University, United States
- University of Colorado, United States
Abstract
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'TR 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.
Data availability
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Differential 3' Processing of Specific Transcripts Expands Regulatory and Protein Diversity Across Neuronal Cell TypesPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE108480).
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MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous systemPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE42880).
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Role of Tet1/3 Genes and Chromatin Remodeling Genes in Cerebellar Circuit FormationPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE74402).
Article and author information
Author details
Funding
National Institutes of Health (NS034389)
- Robert B Darnell
Howard Hughes Medical Institute
- Robert B Darnell
Simons Foundation (SFARI 240432)
- Robert B Darnell
National Institute of Dental and Craniofacial Research (K99DE026823)
- Eric Van Otterloo
National Institutes of Health (NS081706)
- Robert B Darnell
National Institutes of Health (NS097404)
- Robert B Darnell
National Institutes of Health (1UM1HG008901)
- Robert B Darnell
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Bin Tian, Rutgers University New Jersey Medical School, United States
Ethics
Animal experimentation: Animals were maintained in an AAALAC-approved animal facility and all procedures were performed in accordance with IACUC guidelines (protocol number 17013).
Version history
- Received: December 12, 2017
- Accepted: March 20, 2018
- Accepted Manuscript published: March 26, 2018 (version 1)
- Version of Record published: April 13, 2018 (version 2)
Copyright
© 2018, Jereb et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Differential 3' processing of specific transcripts expands regulatory and protein diversity across neuronal cell types
eLife 7:e34042.
https://doi.org/10.7554/eLife.34042
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