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Mol Cell. 2015 Apr 16;58(2):353-61. doi: 10.1016/j.molcel.2015.03.006. Epub 2015 Apr 9.

HOTAIR forms an intricate and modular secondary structure.

Author information

1
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511, USA.
2
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
3
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511, USA; Department of Chemistry, Yale University, New Haven, CT 06511, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: anna.pyle@yale.edu.

Abstract

Long noncoding RNAs (lncRNAs) have recently emerged as key players in fundamental cellular processes and diseases, but their functions are poorly understood. HOTAIR is a 2,148-nt-long lncRNA molecule involved in physiological epidermal development and in pathogenic cancer progression, where it has been demonstrated to repress tumor and metastasis suppressor genes. To gain insights into the molecular mechanisms of HOTAIR, we purified it in a stable and homogenous form in vitro, and we determined its functional secondary structure through chemical probing and phylogenetic analysis. The HOTAIR structure reveals a degree of structural organization comparable to well-folded RNAs, like the group II intron, rRNA, or lncRNA steroid receptor activator. It is composed of four independently folding modules, two of which correspond to predicted protein-binding domains. Secondary structure elements that surround protein-binding motifs are evolutionarily conserved. Our work serves as a guide for "navigating" through the lncRNA HOTAIR and ultimately for understanding its function.

PMID:
25866246
PMCID:
PMC4406478
DOI:
10.1016/j.molcel.2015.03.006
[Indexed for MEDLINE]
Free PMC Article
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