Lin28a Regulates Neuronal Differentiation and Controls MiR-9 Production

Overview

Journal Nat Commun

Specialty Biology

Date 2014 Apr 12

PMID 24722317

Citations 37

Authors

Jakub S Nowak

Nila Roy Choudhury

Flavia de Lima Alves

Juri Rappsilber

Gracjan Michlewski

Affiliations

Soon will be listed here.

Abstract

microRNAs shape the identity and function of cells by regulating gene expression. It is known that brain-specific miR-9 is controlled transcriptionally; however, it is unknown whether post-transcriptional processes contribute to establishing its levels. Here we show that miR-9 is regulated transcriptionally and post-transcriptionally during neuronal differentiation of the embryonic carcinoma cell line P19. We demonstrate that miR-9 is more efficiently processed in differentiated than in undifferentiated cells. We reveal that Lin28a affects miR-9 by inducing the degradation of its precursor through a uridylation-independent mechanism. Furthermore, we show that constitutively expressed untagged but not GFP-tagged Lin28a decreases differentiation capacity of P19 cells, which coincides with reduced miR-9 levels. Finally, using an inducible system we demonstrate that Lin28a can also reduce miR-9 levels in differentiated P19 cells. Together, our results shed light on the role of Lin28a in neuronal differentiation and increase our understanding of the mechanisms regulating the level of brain-specific microRNAs.

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