Molecular anatomy and plasticity of the long noncoding RNA HOTAIR

Abstract

Long noncoding RNA molecules (lncRNAs) are estimated to account for the majority of eukaryotic genomic transcripts, and have been associated with multiple diseases in humans. However, our understanding of their structure-function relationships is scarce, with structural evidence coming mostly from indirect biochemical approaches or computational predictions. Here we describe the hypothetical molecular anatomy of the lncRNA HOTAIR (HOx Transcript AntIsense RNA) inferred from direct, high-resolution visualization by atomic force microscopy (AFM) in nucleus-like conditions at 37 degrees. Our observations reveal that HOTAIR has a distinct anatomy with a high degree of plasticity. Fast AFM scanning enabled the quantification of this plasticity, and provided visual evidence of physical interactions with genomic DNA segments. Our report provides the first biologically-plausible hypothetical description of the anatomy and intrinsic properties of HOTAIR, and presents a framework for studying the structural biology of lncRNAs.