RNase III-independent microRNA biogenesis in mammalian cells

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 e...

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Veröffentlicht in:RNA (Cambridge) 2012-12, Vol.18 (12), p.2166-2173
Hauptverfasser: Maurin, Thomas, Cazalla, Demián, Yang, Jr, Shiuan, Bortolamiol-Becet, Diane, Lai, Eric C
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container_issue 12
container_start_page 2166
container_title RNA (Cambridge)
container_volume 18
creator Maurin, Thomas
Cazalla, Demián
Yang, Jr, Shiuan
Bortolamiol-Becet, Diane
Lai, Eric C
description 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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subjects Animals
Argonaute Proteins - deficiency
Argonaute Proteins - genetics
Argonaute Proteins - metabolism
Base Sequence
Cell Line
DEAD-box RNA Helicases - deficiency
DEAD-box RNA Helicases - genetics
DEAD-box RNA Helicases - metabolism
Endoribonucleases - deficiency
Endoribonucleases - genetics
Endoribonucleases - metabolism
Gene Knockout Techniques
HEK293 Cells
HeLa Cells
Herpesvirus 2, Saimiriine - genetics
Herpesvirus 2, Saimiriine - metabolism
Humans
Mice
MicroRNAs - biosynthesis
MicroRNAs - genetics
Ribonuclease III - deficiency
Ribonuclease III - genetics
Ribonuclease III - metabolism
RNA, Small Nuclear - genetics
RNA, Small Nuclear - metabolism
RNA, Viral - genetics
RNA, Viral - metabolism
title RNase III-independent microRNA biogenesis in mammalian cells
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