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Conserved pseudoknots in lncRNA MEG3 are essential for stimulation of the p53 pathway

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Item Type:Article
Title:Conserved pseudoknots in lncRNA MEG3 are essential for stimulation of the p53 pathway
Creators Name:Uroda, T. and Anastasakou, E. and Rossi, A. and Teulon, J.M. and Pellequer, J.L. and Annibale, P. and Pessey, O. and Inga, A. and Chillón, I. and Marcia, M.
Abstract:Long non-coding RNAs (lncRNAs) are key regulatory molecules, but unlike with other RNAs, the direct link between their tertiary structure motifs and their function has proven elusive. Here we report structural and functional studies of human maternally expressed gene 3 (MEG3), a tumor suppressor lncRNA that modulates the p53 response. We found that, in an evolutionary conserved region of MEG3, two distal motifs interact by base complementarity to form alternative, mutually exclusive pseudoknot structures ("kissing loops"). Mutations that disrupt these interactions impair MEG3-dependent p53 stimulation in vivo and disrupt MEG3 folding in vitro. These findings provide mechanistic insights into regulation of the p53 pathway by MEG3 and reveal how conserved motifs of tertiary structure can regulate lncRNA biological function.
Keywords:RNA Structure, p53 Stress Response, Pituitary Adenoma, Imprinting, RNA Pseudoknots, Alternative Splicing, Atomic Force Microscopy, Epigenetics, RNA Evolution, Cell Cycle Regulation
Source:Molecular Cell
ISSN:1097-2765
Publisher:Cell Press (U.S.A.)
Volume:75
Number:5
Page Range:982-995
Date:5 September 2019
Official Publication:https://doi.org/10.1016/j.molcel.2019.07.025
PubMed:View item in PubMed

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