Health

Tracking mRNA lifespan and myriad functions-ScienceDaily

Despite a pandemic, the successful deployment of mRNA vaccines to combat the SARS-Cov-2 virus has centralized the important role of messenger RNA in all functions of life over the past year. Played a role.

In two new papers published the week of January 17, Wendy Gilbert’s lab at Yale University reveals how mRNA is born and regulates intracellular protein production as it matures. I am doing it. The findings have implications not only for achieving effective doses for new vaccines, but also for helping identify the biological sources of many cancers and illnesses.

Gilbert, an associate professor of molecular biophysics and biochemistry, said:

In classical textbook biology, cells accurately copy or transcribe genes encoded in DNA into mRNA, and ribosomes are intracellular machines that produce proteins that perform almost all vital functions. To do. This important role of mRNA has been a major research subject for decades, including studies that have led to the rapid development of mRNA vaccines in the fight against COVID-19. The vaccine developed by Pfizer and Moderna contains mRNA-based instructions for cells to produce proteins that recognize peplomer proteins on the surface of the SARS-Cov-2 virus and are disrupted by the immune system. It is a target.

RNA is formed from only four bases or nucleotides, but its structure and function can be altered by complex biochemical interactions with other compounds. One such compound that modifies mRNA is pseudouridine, the presence of which is a key isomer of the efficacy of mRNA vaccines. Even before the pandemic, Gilbert’s lab discovered the presence of pseudouridine in the mRNA of normal cells. At that time, she was curious about how these mRNA modifications were created exactly and how they affect the function of mRNA.

In one of the new studies, a team led by Nicole Martinez, a postdoctoral fellow in Gilbert’s lab, discovered that pseudouridine plays an important role in the production of mRNA. The team discovered the presence of pseudouridine in the early stages of mRNA formation. And researchers have found evidence that it leads to splicing of the genetic material that produces mRNA, which in turn regulates gene activity, they report January 19 in the journal Molecular Cell.

These findings shed new light on the origin of diseases associated with pseudouridine variants, such as mitochondrial myopathy, digestive disorders, intellectual disability, and resistance to viral infections. For example, some cancers are associated with elevated levels of pseudouridine, suggesting that false splicing of mRNA can lead to tumorigenesis and cancer metastasis.

Second paper published in the journal on January 17th Cell systemResearchers at Yale University investigated how the ribosome knows how many proteins it produces from the genetic instructions it receives from mRNA. In this study, a team led by Rachel Niederer, a quasi-research scientist in Gilbert’s lab, has developed a new technique called direct analysis of ribosome targeting (DART) that regulates the production of proteins by ribosomes. I found the element. By manipulating such elements with mRNA (in this case, in yeast), scientists were able to change protein production by a factor of 1000, they report.

Researchers say that the ability to accurately manipulate protein production can be immediately applied to adjust the dose of mRNA vaccines, such as those used to combat COVID. Their work led to a $ 1.7 million grant from Pfizer to the Gilbert Institute and a grant from Carson Thoreen, an associate professor of cellular and molecular physiology at Yale University.

However, Gilbert emphasized that the technology can also be applied to the development of protein-based therapies for many diseases.

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material Provided by Yale University.. Original written by Bill Hathaway. Note: Content can be edited in style and length.

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