A recent study conducted by researchers at UC Santa Cruz has uncovered a peptide in human RNA that has the potential to regulate inflammation and could potentially offer new treatment options for diseases like arthritis and lupus. This discovery was made by utilizing the gene-editing tool CRISPR to investigate the mysteries surrounding RNA, the molecule responsible for carrying out genetic information stored in our DNA. The peptide was found within a long non-coding RNA (lncRNA) called LOUP, one of over 20,000 lncRNAs encoded by the human genome. Despite the abundance of lncRNAs, their role and significance remain largely unknown, earning them the nickname “dark matter of the genome.”
Published in the Proceedings of the National Academy of Sciences, this study is one of the few that aims to unravel the complexities of lncRNA. The research offers a new approach to high-throughput screening, allowing researchers to quickly identify functional lncRNAs in immune cells. By utilizing a pooled-screen method, thousands of genes can be targeted in a single experiment, streamlining the study of unexplored areas of the genome compared to traditional, one-gene-at-a-time experiments. Led by immunologist Susan Carpenter, the study focuses on understanding the role of lncRNAs in inflammation and how they influence the immune response.
Carpenter’s research is centered around identifying lncRNAs involved in regulating inflammation, a key feature of many diseases. By studying lncRNAs in monocytes, a type of white blood cell, Carpenter’s team used CRISPR inhibition to repress gene transcription and determine which lncRNAs play a role in monocyte differentiation into macrophages. Unexpectedly, they discovered a region that not only functions as an lncRNA but also contains a previously unknown peptide that regulates inflammation. This finding provides drug developers with a potential target for blocking the molecular interactions responsible for inflammatory responses, offering more precise treatment options compared to targeting proteins expressed throughout the body.
Co-authors of the study from UC Santa Cruz, along with researchers from UCSF and MIT, collaborated to explore the potential of lncRNA in regulating inflammation and immune response. With support from grants from the National Institute of General Medical Sciences and the National Institute of Allergy and Infectious Diseases, the team was able to uncover a novel pathway for potential therapeutic interventions. This discovery opens up new avenues for developing RNA therapeutics that can precisely target specific interactions and pathways responsible for inflammation, paving the way for more effective and targeted treatments for various diseases.
Overall, the study sheds light on the critical role of lncRNAs in regulating inflammation and immune response, offering a new strategy for identifying functional lncRNAs in immune cells. By uncovering a peptide within the lncRNA LOUP that influences inflammation, the researchers have provided valuable insights into potential therapeutic targets for treating inflammatory diseases like arthritis and lupus. This discovery highlights the importance of exploring the “dark matter of the genome” to unlock new possibilities for precision medicine and targeted therapies tailored to specific molecular interactions and pathways. Further research in this area could lead to breakthroughs in treating diseases that involve inflammation as a central component, ultimately improving patient outcomes and quality of life.
