Mammalian DIS3L2 exoribonuclease targets the uridylated precursors of let-7 miRNAs.

Abstract

The mechanisms of gene expression regulation by miRNAs have been extensively studied. However, the regulation of miRNA function and decay has long remained enigmatic. Only recently, 3' uridylation via LIN28A-TUT4/7 has been recognized as an essential component controlling the biogenesis of let-7 miRNAs in stem cells. Although uridylation has been generally implicated in miRNA degradation, the nuclease responsible has remained unknown. Here, we identify the Perlman syndrome-associated protein DIS3L2 as an oligo(U)-binding and processing exoribonuclease that specifically targets uridylated pre-let-7 in vivo. This study establishes DIS3L2 as the missing component of the LIN28-TUT4/7-DIS3L2 pathway required for the repression of let-7 in pluripotent cells.

• Authors: Dmytro Ustianenko, Dominika Hrossova, David Potesil, Katerina Chalupnikova, Kristyna Hrazdilova, Jiri Pachernik, Katerina Cetkovska, Stjepan Uldrijan, Zbynek Zdrahal, Stepanka Vanacova
• Journal: RNA (New York, N.Y.) (RNA) Vol. 19 Issue 12 Pg. 1632-8 (Dec 2013) ISSN: 1469-9001 [Electronic] United States
• PMID: 24141620 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MicroRNAs
• RNA Precursors
• RNA, Small Interfering
• mirnlet7 microRNA, human
• DIS3L2 protein, human
• Exoribonucleases

Topics

• Animals
• Base Sequence
• Cells, Cultured
• Embryonic Stem Cells (enzymology)
• Exoribonucleases (physiology)
• Gene Knockdown Techniques
• HEK293 Cells
• HeLa Cells
• Humans
• Mice
• MicroRNAs (genetics, metabolism)
• Protein Binding
• RNA Precursors (genetics, metabolism)
• RNA Stability
• RNA, Small Interfering (genetics)