lncRNAs: Insights into their function and mechanics in underlying disorders

Genomes of complex organisms are characterized by the pervasive expression of different types of noncoding RNAs (ncRNAs). lncRNAs constitute a large family of long—arbitrarily defined as being longer than 200 nucleotides—ncRNAs that are expressed throughout the cell and that include thousands of different species. While these new and enigmatic players in the complex transcriptional milieu are encoded by a significant proportion of the genome, their functions are mostly unknown at present. Existing examples suggest that lncRNAs have fulfilled a wide variety of regulatory roles at almost every stage of gene expression. These roles, which encompass signal, decoy, scaffold and guide capacities, derive from folded modular domains in lncRNAs. Early discoveries support a paradigm in which lncRNAs regulate transcription networks via chromatin modulation, but new functions are steadily emerging. Given the biochemical versatility of RNA, lncRNAs may be used for various tasks, including posttranscriptional processing. In addition, long intergenic ncRNAs (lincRNAs) are strongly enriched for trait-associated SNPs, which suggest a new mechanism by which intergenic trait-associated regions might function. Moreover, multiple lines of evidence increasingly link mutations and dysregulations of lncRNAs to diverse human diseases, especially disorders related to aging. In this article, we review the current state of the knowledge of the lncRNA field, discussing what is known about the genomic contexts, biological functions and mechanisms of action of these molecules. We highlight the growing evidence for the importance of lncRNAs in diverse human disorders and the indications that their dysregulations and mutations underlie some aging-related disorders. Finally, we consider the potential medical implications, and future potential in the application of lncRNAs as therapeutic targets and diagnostic markers.