RNA EDITING INDEPENDENT FUNCTIONS OF ADENOSINE DEAMINASES ACTING ON DOUBLE-STRANDED RNA IN HEPATOCELLULAR CARCINOMA

Abstract

ADENOSINE DEAMINASES ACTING ON DOUBLE-STRANDED RNA (DSRNA) (ADARS) IS A FAMILY OF ENZYMES CATALYSING ADENOSINE TO INOSINE CONVERSION (A-TO-I EDITING). IF HAPPENED IN CODING REGIONS, A-TO-I EDITING CAN CAUSE PROTEIN RECODING. RECODING EDITING HAS BEEN REPORTED TO CONTRIBUTE TO HEPATOCELLULAR CARCINOMA (HCC) DEVELOPMENT. HOWEVER A-TO-I EDITING IS MOSTLY ENRICHED IN 3? UNTRANSLATED REGIONS (3?UTRS) AND THE ASSOCIATED FUNCTIONS REMAIN LARGELY UNCLEAR. HERE, WE INVESTIGATED THE REGULATIONS OF ADARS ON TARGET GENES WITH EXTENSIVE 3?UTR EDITING. USING RNA-SEQ AND LUCIFERASE REPORTER ASSAYS, WE IDENTIFIED A NOVEL TUMOR SUPPRESSOR GENE METTL7A (METHYLTRANSFERASE LIKE 7A) AS A BONA FIDE 3?UTR EDITING TARGET OF ADARS. HCC PATIENTS WITH LOWER METTL7A EXPRESSION WERE PREDICTED TO HAVE POORER SURVIVAL PROBABILITY. MORE IMPORTANTLY, WE REVEALED THAT ADARS SUPPRESSED METTL7A EXPRESSION INDEPENDENT OF THEIR RNA EDITING ACTIVITIES BY INTERACTING WITH DICER, WHICH PROMOTES THE EXPRESSION OF MIR-27A THAT