Deconvoluting Cell-Type Specific 3'UTR Isoform Expression in the Adult and Developing Cerebellum

<p>Alternative polyadenylation has been implicated in the regulation of mRNA translation and stability, as well as mRNA and protein localization. However, it is unclear to what extent alternative polyadenylation regulates these processes uniquely in specific cell types. Using a newly developed technique, termed conditionally-tagged poly(A) binding protein-mediated mRNA 3' end retrieval by crosslinking immunoprecipitation (cTag-PAPERCLIP), we discovered significant differences in alternative polyadenylation between granule and Purkinje cells in the mouse cerebellum, as well as between proliferating and adult granule cells. Interestingly, among transcripts that differed in alternative polyadenylation in both these comparisons, many were involved in key neuronal functions. We further characterize one such transcript, Memo1, which changed poly(A) site usage during granule cell development, and was concomitantly downregulated. We show that miR-124 specifically targets the long isoform of Memo1, which provides a mechanism for its downregulation during development. Our findings give insight into the roles for alternative polyadenylation in specific cell types and developmental stages, and help establish a platform for further functional studies.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Thesis

Year

2017

Author dc:creator

• Jereb, Saša

Contributors dc:contributor

• Robert B. Darnell

• alternative polyadenylation
• mRNA stability
• granule cells
• Purkinje cells
• miR-124
• Memo1
• Life Sciences

Repository record dc:identifier

https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/394

OAI identifier oai:identifier

oai:digitalcommons.rockefeller.edu:student_theses_and_dissertations-1410