title: Loop-miRs: active microRNAs generated from single-stranded loop regions.
abstract: 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.
authors.affiliation: Helmholtz-University-Group Molecular RNA Biology & Cancer, German Cancer Research Center, DKFZ, Im Neuenheimer Feld 280, D-69120 Heidelberg.
authors.forename: Julia
authors.initials: J
authors.lastname: Winter
authors.forename: Steffen
authors.initials: S
authors.lastname: Link
authors.forename: Dominik
authors.initials: D
authors.lastname: Witzigmann
authors.forename: Catherina
authors.initials: C
authors.lastname: Hildenbrand
authors.forename: Christopher
authors.initials: C
authors.lastname: Previti
authors.forename: Sven
authors.initials: S
authors.lastname: Diederichs
mesh_terms: D060565:Argonaute Proteins / Q000378:metabolism; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry* / Q000378:metabolism; D009690:Nucleic Acid Conformation; D012322:RNA Precursors / Q000737:chemistry* / Q000378:metabolism
chemical_list: D060565:Argonaute Proteins; D035683:MicroRNAs; D012322:RNA Precursors