Methyltransferase-like protein 16 binds the 3′-terminal triple helix of MALAT1 long noncoding RNA

Abstract

Significance RNA triple helices were deduced to form in vitro almost 60 years ago, yet only three examples from eukaryotic cellular RNAs have been structurally validated. The longest triple helix, the MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) ENE+A (element for nuclear expression with a downstream A-rich tract), presents an opportunity to investigate the biological roles of these enigmatic structures. We have discovered that the MALAT1 triple helix is specifically recognized and bound by METTL16 (methyltransferase-like protein 16). There are two important implications: ( i ) the MALAT1 triple helix is a bona fide structure in the cellular environment and ( ii ) there may exist an undiscovered class of triple-stranded RNA binding proteins. METTL16’s antiproliferative role in Caenorhabditis elegans suggests that the METTL16–MALAT1 complex may contribute to the oncogenic activity of MALAT1.