Jul 8, 2016

An RNA editing/binding-independent gene regulatory mechanism of ADARs and its clinical implication in cancer

BioRxiv : the Preprint Server for Biology
Lihua QiLeilei Chen

Abstract

Adenosine-to-inosine (A-to-I) editing, catalysed by Adenosine DeAminases acting on double-stranded RNA (dsRNA) (ADAR), occurs predominantly in the 3′ untranslated regions (3′UTRs). Here we uncover an unanticipated link between ADARs (ADAR1 and ADAR2) and the expression of target genes undergoing extensive 3′UTR editing. Using METTL7A (Methyltransferase Like 7A), a novel tumor suppressor as an exemplary target gene, we demonstrate that its expression could be repressed by ADARs beyond their RNA editing and dsRNA binding functions. ADARs interact with Dicer to augment the processing of pre-miR-27a to mature miR-27a. Consequently, mature miR-27a targets the METTL7A 3′UTR to repress its expression level. In sum, our study unveils that the extensive 3′UTR editing is merely a footprint of ADAR binding, and is dispensable for the regulation of at least a subset of target genes. Instead, ADARs contribute to cancer progression by regulating cancer-related gene expression through their non-canonical functions independent of RNA editing and dsRNA binding. The functional significance of ADARs is much more diverse than previously appreciated and this gene regulatory function of ADARs is most likely to be of higher importance than the best-s...Continue Reading

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Mentioned in this Paper

Study
Tumor Suppressor Genes
Protein Binding
Untranslated Regions
ADAR
Adenosine
Genes
Regulation of Biological Process
RNA, Double-Stranded
MIRN27A microRNA, human

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