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.
journal_name
Proc Natl Acad Sci U S Aauthors
Hwang HW,Wentzel EA,Mendell JTdoi
10.1073/pnas.0811523106subject
Has Abstractpub_date
2009-04-28 00:00:00pages
7016-21issue
17eissn
0027-8424issn
1091-6490pii
0811523106journal_volume
106pub_type
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