Long noncoding RNA as regulatory switch of protein turnover

ABSTRACT: Long intervening noncoding RNAs (lincRNAs) are prevalent genes with poorly understood functions. Here we discover a pathway of lincRNA-regulated proteolysis. The enhancer-like lincRNA HOTTIP extends the half-life of its binding protein WDR5, a subunit of the MLL H3K4 methylase complex, resulting in increased chromatin occupancy and gene activation. LincRNA-mediated stabilization requires direct RNA-protein interaction in a long RNA context, and blocks turnover at a step after target protein poly-ubiquitination. We elucidate the lincRNA binding interface on WDR5. A WDR5 mutant that selectively abrogates lincRNA binding becomes unstable, and is defective in gene activation, maintenance of histone H3 lysine 4 trimethylation, and embryonic stem cell self renewal. The ability to modulate protei

ORGANISM(S): Mus musculus

SUBMITTER: Kun Qu 

PROVIDER: E-GEOD-36513 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress