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

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

Author information

1
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA.
2
Department of Chemistry, Yale University, New Haven, Connecticut, USA.
3
Howard Hughes Medical Institute, Yale University, New Haven, Connecticut, USA.
4
1] Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA. [2] Department of Chemistry, Yale University, New Haven, Connecticut, USA. [3] Howard Hughes Medical Institute, Yale University, New Haven, Connecticut, USA.
5
1] Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA. [2] Howard Hughes Medical Institute, Yale University, New Haven, Connecticut, USA.

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.

PMID:
24952594
PMCID:
PMC4096706
DOI:
10.1038/nsmb.2844
[Indexed for MEDLINE]
Free PMC Article

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