Loop-miRs: active microRNAs generated from single-stranded loop regions

MicroRNAs (miRNAs) are key mediators of post-transcriptional gene regulation. The miRNA precursors are processed by the endonucleases Drosha and Dicer into a duplex, bound to an Argonaute protein and unwound into two single-stranded miRNAs. Although alternative ways to generate miRNAs have been disc...

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Hauptverfasser: Winter, Julia (VerfasserIn) , Link, Steffen (VerfasserIn) , Witzigmann, Dominik (VerfasserIn) , Hildenbrand, Catherina (VerfasserIn) , Previti, A. Christopher (VerfasserIn) , Diederichs, Sven (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 10 April 2013
In: Nucleic acids research
Year: 2013, Jahrgang: 41, Heft: 10, Pages: 5503-5512
ISSN:1362-4962
DOI:10.1093/nar/gkt251
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/nar/gkt251
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Verfasserangaben:Julia Winter, Steffen Link, Dominik Witzigmann, Catherina Hildenbrand, Christopher Previti and Sven Diederichs
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Zusammenfassung:MicroRNAs (miRNAs) are key mediators of post-transcriptional gene regulation. The miRNA precursors are processed by the endonucleases Drosha and Dicer into a duplex, bound to an Argonaute protein and unwound into two single-stranded miRNAs. Although alternative ways to generate miRNAs have been discovered, e.g. pre-miRNA cleavage by Ago2 or cleavage products of snoRNAs or tRNAs, all known pathways converge on a double-stranded RNA duplex. Exogenous single-stranded siRNAs (ss-siRNAs) can elicit an effective RNA interference reaction; recent studies have identified chemical modifications increasing their stability and activity. Here, we provide first evidence that endogenous, unmodified, single-stranded RNA sequences are generated from single-stranded loop regions of human pre-miRNA hairpins, the so called loop-miRs. Luciferase assays and immunoprecipitation validate loop-miR activity and incorporation into RNA-induced silencing complexes. This study identifies endogenous miRNAs that are generated from single-stranded regions; hence, it provides evidence that precursor-miRNAs can give rise to three distinct endogenous miRNAs: the guide strand, the passenger strand and the loop-miR.
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Beschreibung:Online Resource
ISSN:1362-4962
DOI:10.1093/nar/gkt251