Structural insights into the stabilization of MALAT1 noncoding RNA by a bipartite triple helix

Nat Struct Mol Biol. 2014 Jul;21(7):633-40. doi: 10.1038/nsmb.2844. Epub 2014 Jun 22.

Abstract

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a highly abundant nuclear long noncoding RNA that promotes malignancy. A 3'-stem-loop structure is predicted to confer stability by engaging a downstream A-rich tract in a triple helix, similar to the expression and nuclear retention element (ENE) from the KSHV polyadenylated nuclear RNA. The 3.1-Å-resolution crystal structure of the human MALAT1 ENE and A-rich tract reveals a bipartite triple helix containing stacks of five and four U•A-U triples separated by a C+•G-C triplet and C-G doublet, extended by two A-minor interactions. In vivo decay assays indicate that this blunt-ended triple helix, with the 3' nucleotide in a U•A-U triple, inhibits rapid nuclear RNA decay. Interruption of the triple helix by the C-G doublet induces a 'helical reset' that explains why triple-helical stacks longer than six do not occur in nature.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Pairing
  • Base Sequence
  • Crystallography, X-Ray
  • Humans
  • Hydrogen Bonding
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • RNA Stability*
  • RNA, Long Noncoding / chemistry*
  • RNA, Long Noncoding / metabolism
  • RNA, Long Noncoding / physiology

Substances

  • MALAT1 long non-coding RNA, human
  • RNA, Long Noncoding

Associated data

  • PDB/4PLX