Regulation of pri-miRNA Processing by a Long Noncoding RNA Transcribed from an Ultraconserved Region

Julia Liz, Anna Portela, Marta Soler, Antonio Gómez, Hui Ling, Gracjan Michlewski, George A Calin, Sònia Guil, Manel Esteller

Research output: Contribution to journalArticlepeer-review

Abstract

Noncoding RNAs (ncRNAs) control cellular programs by affecting protein-coding genes, but evidence increasingly points to their involvement in a network of ncRNA-ncRNA interactions. Here, we show that a long ncRNA, Uc.283+A, controls pri-miRNA processing. Regulation requires complementarity between the lower stem region of the pri-miR-195 transcript and an ultraconserved sequence in Uc.283+A, which prevents pri-miRNA cleavage by Drosha. Mutation of the site in either RNA molecule uncouples regulation in vivo and in vitro. We propose a model in which lower-stem strand invasion by Uc.283+A impairs microprocessor recognition and efficient pri-miRNA cropping. In addition to identifying a case of RNA-directed regulation of miRNA biogenesis, our study reveals regulatory networks involving different ncRNA classes of importance in cancer.

Original languageEnglish
Pages (from-to)138-47
Number of pages10
JournalMolecular Cell
Volume55
Issue number1
DOIs
Publication statusPublished - 5 Jun 2014

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