title: Structural insights into the stabilization of MALAT1 noncoding RNA by a bipartite triple helix.
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.
authors: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA.
authors: Jessica A
authors: JA
authors: Brown
authors: Department of Chemistry, Yale University, New Haven, Connecticut, USA.
authors: David
authors: D
authors: Bulkley
authors: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA.
authors: Jimin
authors: J
authors: Wang
authors: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA.
authors: Max L
authors: ML
authors: Valenstein
authors: Howard Hughes Medical Institute, Yale University, New Haven, Connecticut, USA.
authors: Therese A
authors: TA
authors: Yario
authors: 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.
authors: Thomas A
authors: TA
authors: Steitz
authors: 1] Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA. [2] Howard Hughes Medical Institute, Yale University, New Haven, Connecticut, USA.
authors: Joan A
authors: JA
authors: Steitz
mesh_terms: D020029:Base Pairing; D001483:Base Sequence; D018360:Crystallography, X-Ray; D006801:Humans; D006860:Hydrogen Bonding; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D020871:RNA Stability; D062085:RNA, Long Noncoding / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology
chemical_list: C557041:MALAT1 long non-coding RNA, human; D062085:RNA, Long Noncoding