The Long Non-coding RNA lnc-31 Interacts with Rock1 mRNA and Mediates Its YB-1-Dependent Translation

Abstract

Summary: Cytoplasmic long non-coding RNAs have been shown to act at many different levels to control post-transcriptional gene expression, although their role in translational control is poorly understood. Here, we show that lnc-31, a non-coding RNA required for myoblast proliferation, promotes ROCK1 protein synthesis by stabilizing its translational activator, YB-1. We find that lnc-31 binds to the Rock1 mRNA as well as to the YB-1 protein and that translational activation requires physical interaction between the two RNA species. These results suggest a localized effect of YB-1 stabilization on the Rock1 mRNA. ROCK1 upregulation by lnc-31, in proliferative conditions, correlates well with the differentiation-repressing activity of ROCK1. We also show that, upon induction of differentiation, the downregulation of lnc-31, in conjunction with miR-152 targeting of Rock1, establishes a regulatory loop that reinforces ROCK1 repression and promotes myogenesis. : Dimartino et al. demonstrate that lnc-31 is required to sustain myoblast proliferation. lnc-31 interacts with Rock1 mRNA, an inhibitor of differentiation, and promotes its translation. This activity is strengthened by binding of the translational regulator YB-1 and its lnc-31-dependent stabilization. Keywords: long non-coding RNA, myogenesis, Rock1, YB-1, lnc-31, cell cycle, translation, proteasome, protein stability