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. An international team led by researchers at the European Molecular Biology Laboratory, Grenoble (EMBL) report structural and functional studies of human maternally expressed gene 3 (MEG3), a tumor suppressor lncRNA that modulates the p53 response. They 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.
Uroda T, Anastasakou E, Rossi A, Teulon JM, Pellequer JL, Annibale P, Pessey O, Inga A, Chillón I, Marcia M. (2019) Conserved Pseudoknots in lncRNA MEG3 Are Essential for Stimulation of the p53 Pathway. Mol Cell 75(5):982-995.e9. [article]
Tagged with: alternative splicing atomic force microscopy cell cycle regulation EMBL epigenetics European Molecular Biology Laboratory Imprinting p53 stress response pituitary adenoma RNA evolution RNA pseudoknots RNA structure