Long noncoding RNAs (lncRNAs) are large transcripts (more than 200 nucleotides long) that have similar mechanism of synthesis as that of mRNAs but unlike mRNAs, lncRNAs are not translated to a protein. lncRNA contains interactor elements and structural elements. Interactor elements directly interact with other nucleic acids or proteins while the structural elements indicate the ability of some lncRNAs to form secondary and/or tertiary structures. This ability of the lncRNAs to interact with nucleic acids using its interactor elements and its ability to interact with protein using its secondary structures allows it to function in a more diverse manner than other ncRNAs such as miRNA (microRNA). LncRNA has been established to play a role in gene regulation by influencing the ability of specific regions of the gene to bind to transcriptional elements and different epigenetic modifications. One such example can be seen in the case X inactive specific transcript (XIST). In humans, 46,XX females carry an extra X chromosome (155Mb of DNA) compared to 46,XY males. To overcome this dosage imbalance, one X chromosome is randomly inactivated in human females at around the 2-8 cell stage of embryo development. This inactivation is very stable across cell divisions due to epigenetic contributions both during the initial silencing and the subsequent maintenance of the inactive X chromosome (Xi). This inactivation is carried by the lncRNA, XIST. XIST is produced in cis and inactivates the X-chromosome that it has been generated from. The inactive X chromosome can be observed as a condensed heterochromatin structure called “Barr Body”.
A study in 2013 utilized this ability of XIST as a potential therapeutic approach for treatment of trisomy 21. Trisomy 21 is commonly known as down syndrome and is caused due to presence of an additional copy of chromosome 21. The study was one of its kind as no other studies have been able to incorporate the XIST gene into a chromosome due to its large size. The study incorporated the XIST into one of the chromosomes 21 in the cells gathered from patients with down syndrome. The study was able to observe the inactivation of one of chromosome 21 in the form of a condensed heterochromatin and labeled it as a chromosome 21 barr body. Such experiments have shown to work in cells in the lab setting although no lncRNA based therapeutics are in clinical trials. The implications of such work can bring trisomy 21 and other chromosomal disorders in the realm of consideration for future gene therapy research.