” Based on our research study, we think easy blood tests for these proteins could provide an important screen for specific cancers and other human diseases,” stated Griffith, the Kenan Distinguished Professor of Microbiology and Immunology and member of the UNC Lineberger Comprehensive Cancer Center. “These tests likewise might offer a measure of telomere health, since we understand telomeres reduce with age.”
Telomeres contain a distinct DNA series including unlimited repeats of TTAGGG bases that in some way hinder chromosomes from staying with each other. Twenty years ago, the Griffith laboratory showed that the end of a telomeres DNA loops back on itself to form a small circle, therefore concealing the end and obstructing chromosome-to-chromosome combinations. When cells divide, telomeres shorten, eventually ending up being so short that the cell can no longer divide appropriately, causing cell death.
Researchers initially recognized telomeres about 80 years ago, and because of their boring sequence, the recognized dogma in the field held that telomeres might not encode for any proteins, let alone ones with powerful biological function.
In 2011 a group in Florida working on an acquired form of ALS reported that the culprit was an RNA molecule including a six-base repeat which by a novel mechanism could generate a series of toxic proteins consisting of two amino acids repeating one after the other. Al-Turki and Griffith note in their paper a striking resemblance of this RNA to the RNA created from human telomeres, and they hypothesized that the same novel mechanism might be in play.
They performed experiments– as explained in the PNAS paper– to demonstrate how telomeric DNA can advise the cell to produce signaling proteins they described VR (valine-arginine) and GL (glycine-leucine). Signaling proteins are basically chemicals that activate a chain reaction of other proteins inside cells that then cause a biological function crucial for health or disease.
Al-Turki and Griffith then chemically synthesized VR and GL to analyze their properties using powerful electron and confocal microscopic lens together with advanced biological methods, revealing that the VR protein is present in elevated quantities in some human cancer cells, along with cells from clients suffering from diseases arising from defective telomeres.
” We believe its possible that as we age, the amount of VR and GL in our blood will steadily rise, possibly providing a brand-new biomarker for biological age as contrasted to sequential age,” stated Al-Turki, a postdoctoral researcher in the Griffith laboratory. “We think swelling might likewise activate the production of these proteins.”
Griffith kept in mind, “When you go versus existing thinking, you are generally incorrect since you are bucking lots of people whove worked so vigilantly in their fields. But occasionally researchers have stopped working to put observations from two really distant fields together and thats what we did. Finding that telomeres encode two novel signaling proteins will alter our understanding of cancer, aging, and how cells communicate with other cells.
” Many questions stay to be answered, but our biggest priority now is developing an easy blood test for these proteins. This might notify us of our biological age and likewise provide warnings of problems, such as cancer or swelling.”
Recommendation: “Mammalian telomeric RNA (TERRA) can be equated to produce valine– arginine and glycine– leucine dipeptide repeat proteins” by Taghreed M. Al-Turki and Jack D. Griffith, 22 February 2023, Proceedings of the National Academy of Sciences.DOI: 10.1073/ pnas.2221529120.
The research study was funded by the National Institutes of Health. The UNC Viral Vector Core and the light microscopy center at the UNC Lineberger Comprehensive Cancer Center were essential partners in this research. Jack Griffith has a joint professors appointment in the UNC Department of Biochemistry and Biophysics.
Freshly discovered telomeric protein VR, (green spheres) is seen collecting in nuclei (blue ovals) in human osteosarcoma cancer cells stained in red. Credit: Griffith Lab, UNC Lineberger
Scientist Jack Griffith and Taghreed Al-Turki from the UNC School of Medicine have found that telomeres, situated at the ends of chromosomes, possess sufficient genetic details to produce two small proteins with possibly potent biological properties.
Telomeres, formerly thought to be incapable of encoding proteins due to their repeated DNA series, have actually now been discovered to hold a powerful biological function that may have substantial implications for our understanding of cancer and aging.
In a research study published in the Proceedings of the National Academy of Science, Taghreed Al-Turki, Ph.D., and Jack Griffith, Ph.D., from the UNC School of Medicine, made a remarkable finding that telomeres include genetic info to produce two little proteins. The researchers discovered that a person of these proteins rises in some human cancer cells and cells from clients with telomere-related flaws.
2 decades ago, the Griffith laboratory showed that the end of a telomeres DNA loops back on itself to form a small circle, hence concealing the end and obstructing chromosome-to-chromosome blends. When cells divide, telomeres reduce, eventually ending up being so brief that the cell can no longer divide appropriately, leading to cell death.
Griffith kept in mind, “When you go versus current thinking, you are usually incorrect since you are bucking numerous people whove worked so diligently in their fields. Discovering that telomeres encode 2 novel signaling proteins will change our understanding of cancer, aging, and how cells interact with other cells.
Jack Griffith has a joint professors visit in the UNC Department of Biochemistry and Biophysics.
