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

Research output: Contribution to journalJournal articleResearchpeer-review

  • 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.
Original languageEnglish
JournalNature Structural and Molecular Biology
Volume18
Issue number9
Pages (from-to)1075–1082
Number of pages8
ISSN1545-9993
DOIs
Publication statusPublished - 2011

ID: 33877164