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Structure–function relationship of long noncoding RNAs: Advances and challenges

Long noncoding RNAs (lncRNAs) are an emerging and a promising class of RNAs, and the lncRNA field is an intense research area. Once trashed as the junk regions of the genome, lncRNAs have now proved to be one of the crucial elements of a functional genome. These comprise a major chunk of the transcriptome, and similar to proteins, the sequence–structure–function paradigm holds true for lncRNAs as well. While some of the earliest lncRNAs like Xist and H19 have been well‐characterized, many of the emerging lncRNAs remain in oblivion. The low sequence conservation of lncRNAs has prompted researchers to decipher its conserved structure in order to gain an insight into the functional mechanisms. Here, we explore the concept of the sequence–structure–function relationship of lncRNAs, and the biophysical and biochemical laws governing a lncRNA structure which are just beginning to be understood. Proceeding from specific structures, much of the functions of lncRNAs revolve around their regulatory roles, through myriad modes of action. Throughout this review, we discuss the powerful computational as well as some experimental approaches that are applied in a synergistic fashion and highlight promising studies that have proved crucial towards an understanding of lncRNA structure and functional mechanisms. We also discuss at length, the existing challenges and the possible strategies to circumvent it. Given the unknown realm, the patterns and insights generated from these studies will be extremely useful in deciphering the way nature selects and uses a specific lncRNA to regulate a specific gene or gene sets in health and disease.