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

Tina Uroda, Eleni Anastasakou, Annalisa Rossi, Jean Marie Teulon, Jean-Luc Pellequer, Paolo Annibale, Ombeline Pessey, Alberto Inga, Isabel Chillón*, Marco Marcia

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

67 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)982-995
Number of pages24
JournalMolecular Cell
Volume75
Issue number5
Early online date20 Aug 2019
DOIs
Publication statusPublished - 5 Sept 2019

Keywords

  • Alternative splicing
  • Atomic force microscopy
  • Cell cycle regulation
  • Epigenetics
  • Imprinting
  • p53 stress response
  • Pituitary adenoma
  • RNA evolution
  • RNA pseudoknots
  • RNA structure

Fingerprint

Dive into the research topics of 'Conserved pseudoknots in lncRNA MEG3 are essential for stimulation of the p53 pathway'. Together they form a unique fingerprint.

Cite this