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

Author

Saša Jereb

Date of Award

2017

Document Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

RU Laboratory

Darnell Robert Laboratory

Abstract

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.

Comments

A Thesis Presented to the Faculty of The Rockefeller University in Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy

Recommended Citation

Jereb, Saša, "Deconvoluting Cell-Type Specific 3'UTR Isoform Expression in the Adult and Developing Cerebellum" (2017). Student Theses and Dissertations. 394.
https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/394