Cell-cell contact globally activates microRNA biogenesis.

Abstract:

:MicroRNAs (miRNAs) are 18- to 24-nt RNA molecules that regulate messenger RNAs (mRNAs). Posttranscriptional mechanisms regulate miRNA abundance during development as well as in cancer cells where miRNAs frequently exhibit dysregulated expression. The molecular mechanisms that govern the global efficiency of miRNA biogenesis in these settings remain incompletely understood, and experimental systems for the biochemical dissection of these pathways are currently lacking. Here, we demonstrate that miRNAs are subject to dynamic posttranscriptional regulation in widely used cell culture systems. As diverse mammalian and Drosophila cell lines are grown to increasing density, miRNA biogenesis is globally activated, leading to elevated mature miRNA levels and stronger repression of target constructs. This broad increase in miRNA abundance is associated with enhanced processing of miRNAs by Drosha and more efficient formation of RNA-induced silencing complexes. These findings uncover a critical parameter necessary for accurate analysis of miRNAs in cell culture settings, establish a tractable system for the study of regulated miRNA biogenesis, and may provide insight into mechanisms that influence miRNA expression in physiologic and pathophysiologic states.

authors

Hwang HW,Wentzel EA,Mendell JT

doi

10.1073/pnas.0811523106

subject

Has Abstract

pub_date

2009-04-28 00:00:00

pages

7016-21

issue

17

eissn

0027-8424

issn

1091-6490

pii

0811523106

journal_volume

106

pub_type

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