The Long Non-coding RNA lnc-31 Interacts with Rock1 mRNA and Mediates Its YB-1-Dependent Translation
Dacia Dimartino,
Alessio Colantoni,
Monica Ballarino,
Julie Martone,
Davide Mariani,
Johannes Danner,
Astrid Bruckmann,
Gunter Meister,
Mariangela Morlando,
Irene Bozzoni
Affiliations
Dacia Dimartino
Department of Biology and Biotechnology, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy
Alessio Colantoni
Department of Biology and Biotechnology, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy
Monica Ballarino
Department of Biology and Biotechnology, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy
Julie Martone
Department of Biology and Biotechnology, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy
Davide Mariani
Department of Biology and Biotechnology, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy
Johannes Danner
Biochemistry Center Regensburg, Laboratory for RNA Biology, University of Regensburg, 93053 Regensburg, Germany
Astrid Bruckmann
Biochemistry Center Regensburg, Laboratory for RNA Biology, University of Regensburg, 93053 Regensburg, Germany
Gunter Meister
Biochemistry Center Regensburg, Laboratory for RNA Biology, University of Regensburg, 93053 Regensburg, Germany
Mariangela Morlando
Department of Biology and Biotechnology, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy; Corresponding author
Irene Bozzoni
Department of Biology and Biotechnology, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy; Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Viale Regina Elena 291, 00161 Rome, Italy; Institute Pasteur Fondazione Cenci-Bolognetti, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy; Corresponding author
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
