"Dark matter" on Chromosomes Discovered: Prof. Wang Honglin's Team From Shanghai General Hospital of Jiao Tong University School of Medicine Revealed a New Code for Immune Regulation on the Genome

https://mp.weixin.qq.com/s/GgAHjhQDZwZrUKTKOTHyBw

On January 30, 2024, Honglin Wang's team from Shanghai General Hospital of Shanghai Jiao Tong University School of Medicine published a research paper entitled "A lncRNA Dleu2-encoded peptide relieves autoimmunity by facilitating Smad3-mediated Treg induction" in EMBO Reports. In this study, an endogenous small peptide Dleu2-17aa composed of 17 amino acids was discovered and identified in the long non-coding RNA Dleu2 by ribosome fingerprint, mass spectrum, and protein in vitro binding. Dleu2-17aa has been shown to promote Treg differentiation and treat autoimmune diseases in mouse models through this mechanism.

The human genome contains about 3 trillion DNA nucleotides, of which transcripts cover 62-75% of the genome1, and only 2% are involved in coding proteins2, and for a long time, up to 98% of DNA sequences do not encode any functional products and are considered "junk DNA", which is contrary to evolutionary theory. However, with the development of science and technology, researchers have found that the "dark matter" on these chromosomes may hide important information about the regulation of life. Among them, long non-coding RNAs (lncRNAs) have attracted extensive attention. In recent years, it has been discovered that some lncRNAs can encode short peptides that are involved in the regulation of various cellular activities. However, the effects and mechanisms of such small peptides have been reported in immune cells relatively rarely.

Honglin Wang's team has been deeply engaged in this emerging field in recent years, and has continued to discover immune-regulating small peptides from non-coding RNA genes. The continuous discovery of the research group fully demonstrates that non-coding RNA also contains rich regulatory information and potential to treat diseases, which is waiting for us to continue to decipher. These small peptides from the "dark matter" of the genome have fast metabolic properties, high specificity and selectivity, and are easy to synthesize and engineer, providing a reserve and research ideas for the clinical development of innovative drugs for the treatment of a variety of diseases.