Fiche publication
Date publication
avril 2016
Journal
Nucleic acids research
Auteurs
Membres identifiés du Cancéropôle Est :
Dr PFEFFER Sébastien
,
Mr HAMMANN Philippe
Tous les auteurs :
Haas G, Cetin S, Messmer M, Chane-Woon-Ming B, Terenzi O, Chicher J, Kuhn L, Hammann P, Pfeffer S
Lien Pubmed
Résumé
The mechanism by which micro (mi)RNAs control their target gene expression is now well understood. It is however less clear how the level of miRNAs themselves is regulated. Under specific conditions, abundant and highly complementary target RNA can trigger miRNA degradation by a mechanism involving nucleotide addition and exonucleolytic degradation. One such mechanism has been previously observed to occur naturally during viral infection. To date, the molecular details of this phenomenon are not known. We report here that both the degree of complementarity and the ratio of miRNA/target abundance are crucial for the efficient decay of the small RNA. Using a proteomic approach based on the transfection of biotinylated antimiRNA oligonucleotides, we set to identify the factors involved in target-mediated miRNA degradation. Among the retrieved proteins, we identified members of the RNA-induced silencing complex, but also RNA modifying and degradation enzymes. We further validate and characterize the importance of one of these, the Perlman Syndrome 3'-5' exonuclease DIS3L2. We show that this protein interacts with Argonaute 2 and functionally validate its role in target-directed miRNA degradation both by artificial targets and in the context of mouse cytomegalovirus infection.
Mots clés
Animals, Argonaute Proteins, genetics, Base Sequence, Biotinylation, Cell Line, Tumor, Cytomegalovirus, genetics, Cytomegalovirus Infections, genetics, Exoribonucleases, genetics, Gene Expression Regulation, HEK293 Cells, HeLa Cells, Hepatocytes, cytology, Humans, Mice, MicroRNAs, antagonists & inhibitors, Molecular Sequence Data, Nucleotidyltransferases, genetics, Oligonucleotides, Antisense, genetics, RNA Stability, RNA, Messenger, genetics, mRNA Cleavage and Polyadenylation Factors, genetics
Référence
Nucleic Acids Res.. 2016 Apr;44(6):2873-87
