LIN28, a Wilms tumor oncoprotein, triggers the DIS3L2-mediated degradation of the precursor of let-7, a microRNA that inhibits Wilms tumor development.
By selecting focal regions commonly involved in chromosomal anomalies, we identified genes with a possible role in WT development, based on the prior knowledge of their biological relevance, including <i>MYCN, DIS3L2, MIR562</i>, <i>HACE1</i>, <i>GLI3</i>, <i>CDKN2A</i> and <i>CDKN2B</i>, <i>PALB2</i>, and <i>CHEK2</i>.
Our study establishes 3' oligouridylation as an RNA decay signal for Dis3l2, and identifies the first physiological RNA substrate of this new exonuclease, which is mutated in the Perlman syndrome of fetal overgrowth and causes a predisposition to Wilms' tumour development.