Biogenic mechanisms and utilization of small RNAs derived from human protein-coding genes

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Eivind Valen
  • Pascal Preker
  • Peter Refsing Andersen
  • Xiaobei Zhao
  • Yun Chen
  • Christine Ender
  • Anne Dueck
  • Gunter Meister
  • Sandelin, Albin Gustav
  • Torben Heick Jensen
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.
OriginalsprogEngelsk
TidsskriftNature Structural and Molecular Biology
Vol/bind18
Udgave nummer9
Sider (fra-til)1075–1082
Antal sider8
ISSN1545-9993
DOI
StatusUdgivet - 2011

ID: 33877164