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Structural insights into the stabilization of MALAT1 noncoding RNA by a bipartite triple helix
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Structural insights into the stabilization of MALAT1 noncoding RNA by a bipartite triple helix
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Journal Article
Structural insights into the stabilization of MALAT1 noncoding RNA by a bipartite triple helix
2014
Overview
The X-ray crystal structure and biochemical analysis of a triple helix formed between the expression and nuclear retention element (ENE) and the 3′ poly(A) tail of the human long noncoding RNA MALAT-1 reveals the basis of its stability and how it confers resistance to degradation.
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.
Publisher
Nature Publishing Group US,Nature Publishing Group
