title: Adenosine-to-inosine RNA editing meets cancer.
abstract: The role of epigenetics in tumor onset and progression has been extensively addressed. Discoveries in the last decade completely changed our view on RNA. We now realize that its diversity lies at the base of biological complexity. Adenosine-to-inosine (A-to-I) RNA editing emerges a central generator of transcriptome diversity and regulation in higher eukaryotes. It is the posttranscriptional deamination of adenosine to inosine in double-stranded RNA catalyzed by enzymes of the adenosine deaminase acting on RNA (ADAR) family. Thought at first to be restricted to coding regions of only a few genes, recent bioinformatic analyses fueled by high-throughput sequencing revealed that it is a widespread modification affecting mostly non-coding repetitive elements in thousands of genes. The rise in scope is accompanied by discovery of a growing repertoire of functions based on differential decoding of inosine by the various cellular machineries: when recognized as guanosine, it can lead to protein recoding, alternative splicing or altered microRNA specificity; when recognized by inosine-binding proteins, it can result in nuclear retention of the transcript or its degradation. An imbalance in expression of ADAR enzymes with consequent editing dysregulation is a characteristic of human cancers. These alterations may be responsible for activating proto-oncogenes or inactivating tumor suppressors. While unlikely to be an early initiating 'hit', editing dysregulation seems to contribute to tumor progression and thus should be considered a 'driver mutation'. In this review, we examine the contribution of A-to-I RNA editing to carcinogenesis.
authors.affiliation: Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel.
authors.forename: Dan
authors.initials: D
authors.lastname: Dominissini
authors.forename: Sharon
authors.initials: S
authors.lastname: Moshitch-Moshkovitz
authors.forename: Ninette
authors.initials: N
authors.lastname: Amariglio
authors.forename: Gideon
authors.initials: G
authors.lastname: Rechavi
mesh_terms: D000241:Adenosine / Q000737:chemistry / Q000235:genetics*; D000818:Animals; D006801:Humans; D007288:Inosine / Q000737:chemistry / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics*; D017393:RNA Editing
chemical_list: D007288:Inosine; D000241:Adenosine