RNase III-independent microRNA biogenesis in mammalian cells
- 1Department of Developmental Biology, Sloan-Kettering Institute, New York, New York 10065, USA
- 2Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06536, USA
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↵3 These authors contributed equally to this work.
Abstract
RNase III enzymes are fundamental to the biogenesis of microRNAs (miRNAs) and small interfering RNAs (siRNAs) in all species studied. Although alternative miRNA pathways independent of Drosha or Dicer exist, each still requires one RNase III-type enzyme. Here, we describe two strategies that marry either RNase Z or the Integrator complex with the slicing activity of Argonaute2 to generate highly functional mature miRNAs. We provide stringent validation of their RNase III independence by demonstrating efficient miRNA biogenesis and activity in Drosha and Dicer knockout cells. These data provide proof-of-principle evidence for additional mechanistic possibilities for efficient generation of small regulatory RNAs, and represent novel silencing triggers that may be exploited for technical purposes.
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Footnotes
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↵5 Corresponding author
E-mail laie{at}mskcc.org
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Article published online ahead of print. Article and publication date are at http://www.rnajournal.org/cgi/doi/10.1261/rna.036194.112.
- Received August 29, 2012.
- Accepted September 4, 2012.
- Copyright © 2012 RNA Society
