Distinct MUNC lncRNA structural domains regulate transcription of different promyogenic factors

Abstract

Long non-coding RNAs (lncRNA) are a type of RNA that is not translated into protein. Many lncRNAs have been discovered using high-throughput sequencing data; however, it is unclear what fraction of them is functional and what structural properties affect their phenotype. One of the lncRNAs important for skeletal muscle differentiation is MUNC acting in cis as an enhancer RNA for the Myod1 gene and in trans by recruiting the cohesin complex. Here, experimental probing of the RNA structure revealed that MUNC contains multiple structural domains not detected by prediction algorithms in the absence of experimental information. We show that these specific and structurally distinct domains are required for induction of muscle-related genes, for binding genomic sites and gene expression regulation, and for binding the cohesin complex. Our study reveals unexpectedly complex, structure-driven functions for the MUNC and emphasizes the importance of experimentally determined structures for understanding structure-function relationships in lncRNAs.