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 |
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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. |
doi_str_mv | 10.1261/rna.036194.112 |
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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.</description><subject>Animals</subject><subject>Argonaute Proteins - deficiency</subject><subject>Argonaute Proteins - genetics</subject><subject>Argonaute Proteins - metabolism</subject><subject>Base Sequence</subject><subject>Cell Line</subject><subject>DEAD-box RNA Helicases - deficiency</subject><subject>DEAD-box RNA Helicases - genetics</subject><subject>DEAD-box RNA Helicases - metabolism</subject><subject>Endoribonucleases - deficiency</subject><subject>Endoribonucleases - genetics</subject><subject>Endoribonucleases - metabolism</subject><subject>Gene Knockout Techniques</subject><subject>HEK293 Cells</subject><subject>HeLa Cells</subject><subject>Herpesvirus 2, Saimiriine - genetics</subject><subject>Herpesvirus 2, Saimiriine - metabolism</subject><subject>Humans</subject><subject>Mice</subject><subject>MicroRNAs - biosynthesis</subject><subject>MicroRNAs - genetics</subject><subject>Ribonuclease III - deficiency</subject><subject>Ribonuclease III - genetics</subject><subject>Ribonuclease III - metabolism</subject><subject>RNA, Small Nuclear - genetics</subject><subject>RNA, Small Nuclear - metabolism</subject><subject>RNA, Viral - genetics</subject><subject>RNA, Viral - metabolism</subject><issn>1355-8382</issn><issn>1469-9001</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkNtLwzAUxoMobl5efZQ--tKak3tBhDG8FMaEoc8hbdMZadPZbIL_vRmbQ19yO9_5zpcfQleAMyACbgdvMkwF5CwDIEdoDEzkaY4xHMcz5TxVVJEROgvhIz7SWD5FI0JxLhmhY3S3mJtgk6IoUudru7Jx8eukc9XQL-aTpHT90nobXEicTzrTdaZ1xieVbdtwgU4a0wZ7ud_P0dvjw-v0OZ29PBXTySytGBfrVOYKjAXgpGG8wrLJKY6XGA6zUuXUSCFkqVhjFccSSkKIxHXNgVZSMQH0HN3vfFebsrN1FRMOptWrwXVm-Na9cfp_xbt3vey_NI0ThMijwc3eYOg_NzasdefC9gvG234TNIBUQmHOWZRmO2kEEMJgm8MYwHqLXEfkeoc89pHYcP033EH-y5j-AOZxeuw</recordid><startdate>20121201</startdate><enddate>20121201</enddate><creator>Maurin, Thomas</creator><creator>Cazalla, Demián</creator><creator>Yang, Jr, Shiuan</creator><creator>Bortolamiol-Becet, Diane</creator><creator>Lai, Eric C</creator><general>Cold Spring Harbor Laboratory Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20121201</creationdate><title>RNase III-independent microRNA biogenesis in mammalian cells</title><author>Maurin, Thomas ; Cazalla, Demián ; Yang, Jr, Shiuan ; Bortolamiol-Becet, Diane ; Lai, Eric C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c456t-7981ae1152f45c07f93015235504b893a7667b84fe85071b22270dd513c784613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Argonaute Proteins - deficiency</topic><topic>Argonaute Proteins - genetics</topic><topic>Argonaute Proteins - metabolism</topic><topic>Base Sequence</topic><topic>Cell Line</topic><topic>DEAD-box RNA Helicases - deficiency</topic><topic>DEAD-box RNA Helicases - genetics</topic><topic>DEAD-box RNA Helicases - metabolism</topic><topic>Endoribonucleases - deficiency</topic><topic>Endoribonucleases - genetics</topic><topic>Endoribonucleases - metabolism</topic><topic>Gene Knockout Techniques</topic><topic>HEK293 Cells</topic><topic>HeLa Cells</topic><topic>Herpesvirus 2, Saimiriine - genetics</topic><topic>Herpesvirus 2, Saimiriine - metabolism</topic><topic>Humans</topic><topic>Mice</topic><topic>MicroRNAs - biosynthesis</topic><topic>MicroRNAs - genetics</topic><topic>Ribonuclease III - deficiency</topic><topic>Ribonuclease III - genetics</topic><topic>Ribonuclease III - metabolism</topic><topic>RNA, Small Nuclear - genetics</topic><topic>RNA, Small Nuclear - metabolism</topic><topic>RNA, Viral - genetics</topic><topic>RNA, Viral - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Maurin, Thomas</creatorcontrib><creatorcontrib>Cazalla, Demián</creatorcontrib><creatorcontrib>Yang, Jr, Shiuan</creatorcontrib><creatorcontrib>Bortolamiol-Becet, Diane</creatorcontrib><creatorcontrib>Lai, Eric C</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>RNA (Cambridge)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Maurin, Thomas</au><au>Cazalla, Demián</au><au>Yang, Jr, Shiuan</au><au>Bortolamiol-Becet, Diane</au><au>Lai, Eric C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>RNase III-independent microRNA biogenesis in mammalian cells</atitle><jtitle>RNA (Cambridge)</jtitle><addtitle>RNA</addtitle><date>2012-12-01</date><risdate>2012</risdate><volume>18</volume><issue>12</issue><spage>2166</spage><epage>2173</epage><pages>2166-2173</pages><issn>1355-8382</issn><eissn>1469-9001</eissn><abstract>RNase III enzymes are fundamental to the biogenesis of microRNAs (miRNAs) and small interfering RNAs (siRNAs) in all species studied. 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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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