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

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Authors	USTIANENKO Dmytro HROŠŠOVÁ Dominika POTĚŠIL David CHALUPNÍKOVÁ Kateřina HRAZDILOVÁ Kristýna PACHERNÍK Jiří CETKOVSKÁ Kateřina ULDRIJAN Stjepan ZDRÁHAL Zbyněk VAŇÁČOVÁ Štěpánka
Year of publication	2013
Type	Article in Periodical
Magazine / Source	RNA
MU Faculty or unit	Central European Institute of Technology
Citation
Web	http://rnajournal.cshlp.org/content/early/2013/10/18/rna.040055.113.abstract
Doi	http://dx.doi.org/10.1261/rna.040055.113
Field	Genetics and molecular biology
Keywords	DIS3L2; RNA degradation; RNA uridylation; let-7 miRNA
Attached files	Ustianenko_et_al_RNA2013.pdf ZVV_2013_006_1126856_Mammalian.pdf
Description	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 syndromeassociated 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.
Related projects:	Functional and biochemical characterization of Dis3L2, the third mammalian homolog of the key yeast exosome nuclease Dis3p CEITEC - Central European Institute of Technology Centrum nových přístupů k bioanalýze a molekulární diagnostice Centrum biologie RNA