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Differential 3’ processing of specific transcripts expands regulatory and protein diversity across neuronal cell types
Journal article   Open access   Peer reviewed

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

Saša Jereb, Hun-Way Hwang, Eric Van Otterloo, Eve-Ellen Govek, John J Fak, Yuan Yuan, Mary E Hatten and Robert B Darnell
eLife, Vol.7, e34042
03/26/2018
DOI: 10.7554/eLife.34042
PMCID: PMC5898910
PMID: 29578408
url
https://doi.org/10.7554/eLife.34042View
Published (Version of record) Open Access

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’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.
 Cerebellum Neuroscience alternative polyadenylation granule cells Mouse Purkinje cells

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