Lin28a regulates neuronal differentiation and controls miR-9 production

Jakub S. Nowak, Nila Roy Choudhury, Flavia de Lima Alves, Juri Rappsilber and Gracjan Michlewski ()
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Jakub S. Nowak: Wellcome Trust Centre for Cell Biology, University of Edinburgh
Nila Roy Choudhury: Wellcome Trust Centre for Cell Biology, University of Edinburgh
Flavia de Lima Alves: Wellcome Trust Centre for Cell Biology, University of Edinburgh
Juri Rappsilber: Wellcome Trust Centre for Cell Biology, University of Edinburgh
Gracjan Michlewski: Wellcome Trust Centre for Cell Biology, University of Edinburgh

Nature Communications, 2014, vol. 5, issue 1, 1-12

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms4687

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