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- Title
Structural insights into the stabilization of MALAT1 noncoding RNA by a bipartite triple helix.
- Authors
Brown, Jessica A; Bulkley, David; Wang, Jimin; Valenstein, Max L; Yario, Therese A; Steitz, Thomas A; Steitz, Joan A
- 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.
- Subjects
LUNG cancer; METASTASIS; NON-coding RNA; TUMOR growth; CANCER invasiveness; CANCER cell proliferation
- Publication
Nature Structural & Molecular Biology, 2014, Vol 21, Issue 7, p633
- ISSN
1545-9993
- Publication type
Article
- DOI
10.1038/nsmb.2844