title: Biogenic mechanisms and utilization of small RNAs derived from human protein-coding genes.
abstract: Efforts to catalog eukaryotic transcripts have uncovered many small RNAs (sRNAs) derived from gene termini and splice sites. Their biogenesis pathways are largely unknown, but a mechanism based on backtracking of RNA polymerase II (RNAPII) has been suggested. By sequencing transcripts 12-100 nucleotides in length from cells depleted of major RNA degradation enzymes and RNAs associated with Argonaute (AGO1/2) effector proteins, we provide mechanistic models for sRNA production. We suggest that neither splice site-associated (SSa) nor transcription start site-associated (TSSa) RNAs arise from RNAPII backtracking. Instead, SSa RNAs are largely degradation products of splicing intermediates, whereas TSSa RNAs probably derive from nascent RNAs protected by stalled RNAPII against nucleolysis. We also reveal new AGO1/2-associated RNAs derived from 3' ends of introns and from mRNA 3' UTRs that appear to draw from noncanonical microRNA biogenesis pathways.
authors.affiliation: The Bioinformatics Centre, Department of Biology and the Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
authors.forename: Eivind
authors.initials: E
authors.lastname: Valen
authors.forename: Pascal
authors.initials: P
authors.lastname: Preker
authors.forename: Peter Refsing
authors.initials: PR
authors.lastname: Andersen
authors.forename: Xiaobei
authors.initials: X
authors.lastname: Zhao
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
authors.forename: Christine
authors.initials: C
authors.lastname: Ender
authors.forename: Anne
authors.initials: A
authors.lastname: Dueck
authors.forename: Gunter
authors.initials: G
authors.lastname: Meister
authors.forename: Albin
authors.initials: A
authors.lastname: Sandelin
authors.forename: Torben Heick
authors.initials: TH
authors.lastname: Jensen
mesh_terms: D060565:Argonaute Proteins; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D039642:Eukaryotic Initiation Factors / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D005091:Exons; D006367:HeLa Cells; D006801:Humans; D007438:Introns; D035683:MicroRNAs / Q000096:biosynthesis; D012319:RNA Polymerase II / Q000502:physiology; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism; D058727:RNA, Small Untranslated / Q000096:biosynthesis* / Q000737:chemistry; D024363:Transcription Initiation Site
chemical_list: C115848:AGO1 protein, human; C466422:AGO2 protein, human; D060565:Argonaute Proteins; D015852:Eukaryotic Initiation Factor-2; D039642:Eukaryotic Initiation Factors; D035683:MicroRNAs; D012333:RNA, Messenger; D058727:RNA, Small Untranslated; D012319:RNA Polymerase II