The long noncoding RNA <i>SPRIGHTLY</i> acts as an intranuclear organizing hub for pre-mRNA molecules.

Abstract

Molecular mechanisms by which long noncoding RNA (lncRNA) molecules may influence cancerous condition are poorly understood. The aberrant expression of <i>SPRIGHTLY</i> lncRNA, encoded within the drosophila gene homolog <i>Sprouty-4</i> intron, is correlated with a variety of cancers, including human melanomas. We demonstrate by SHAPE-seq and dChIRP that <i>SPRIGHTLY</i> RNA secondary structure has a core pseudoknotted domain. This lncRNA interacts with the intronic regions of six pre-mRNAs: <i>SOX5</i>, <i>SMYD3</i>, <i>SND1</i>, <i>MEOX2</i>, <i>DCTN6</i>, and <i>RASAL2</i>, all of which have cancer-related functions. Hemizygous knockout of <i>SPRIGHTLY</i> by CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 in melanoma cells significantly decreases <i>SPRIGHTLY</i> lncRNA levels, simultaneously decreases the levels of its interacting pre-mRNA molecules, and decreases anchorage-independent growth rate of cells and the rate of in vivo tumor growth in mouse xenografts. These results provide the first demonstration of an lncRNA's three-dimensional coordinating role in facilitating cancer-related gene expression in human melanomas.