UC Santa Cruz researchers have found a peptide in human RNA that controls inflammation and could offer a new approach to treating diseases like arthritis and lupus. They utilized a screening method utilizing the CRISPR gene-editing tool to uncover a major mystery surrounding our RNA, which is responsible for carrying out genetic information from our DNA.Research has utilized the gene-editing tool CRISPR to gain insight into a major mystery surrounding RNA, the molecule responsible for carrying out genetic instructions from DNA. A peptide derived from a long non-coding RNA (lncRNA) called LOUP was the focus of the research. The human genome contains more than 20,000 lncRNAs, making them the largest group of genes produced from the genome. Despite this abundance, there is limited understanding of the reasons for lncRNAs’ existence or their functions, leading to lncRNAs being dubbed the “dark matter of the genome.” The study was published on May 23 in the Proceedings of the National Academy of Sciences.The National Academy of Sciences (PNAS) is one of the few sources that delves into the mysteries of lncRNA. The study also introduces a new method for quickly identifying functional lncRNAs in immune cells through high-throughput screening. This approach allows researchers to target thousands of genes in a single experiment, making it a more efficient way to study uncharacterized parts of the genome compared to traditional experiments that focus on one gene at a time. The research was led by immunologist Susan Carpenter, a professor and Sinsheimer Chair of UC Santa Cruz’s Molecular, Cell, and Developmental Biology Department.The scientist, Dr. Smith, from the Developmental Biology Department, is researching the molecular mechanisms that protect against infections. Her main focus is on understanding the role of lncRNAs in the processes that lead to inflammation, as inflammation is a key feature of many diseases. Dr. Smith’s lab is specifically trying to identify the lncRNA genes that regulate inflammation. To do this, they are studying the lncRNAs in a type of white blood cell called monocytes. They are using a modified version of CRISPR/Cas9 technology, known as CRISPR inhibition (CRISPRi), to repress gene transcription and identify the lncRNA genes involved.identifying the lncRNAs involved in the differentiation of monocytes into macrophages, researchers have used CRISPRi to screen the lncRNA in macrophages for its role in inflammation. Surprisingly, a multifunctional region was discovered, containing an undiscovered peptide that regulates inflammation as well as functioning as an RNA. This newfound understanding of the peptide’s role in regulating inflammation provides drug developers with a target for suppressing the molecular interaction responsible for the inflammatory response.In a perfect world, the goal would be to create a small molecule that could disrupt that specific interaction, rather than targeting a protein that may be present in the entire body,” she said. “We’re still far from being able to target these pathways with that level of precision, but it’s definitely the aim. There’s currently a lot of interest in RNA therapeutics.” Co-authors of the UC Santa Cruz study include Haley Halasz, Eric Malekos, Sergio Covarrubias, Samira Yitiz, Christy Montano, Lisa Sudek, and Sol Katzman, as well as researchers at UCSF and MIT. The research received funding from the National Institute of General Medic.The research was funded by the National Institute of General Medical Sciences (R35GM137801 to Carpenter) and the National Institute of Allergy and Infectious Diseases (F31AI179201 to Malekos).
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