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UMass Amherst assistant professor of microbiology Mandy Muller
In the lengthy-time period battle between a herpesvirus and its human host, a University of Massachusetts Amherst virologist and her group of college students have recognized some human RNA in a position to withstand the viral takeover – and the mechanism by which that happens.
This discovery, described in a paper revealed Feb. 17 in Proceedings of the National Academy of Sciences, represents an essential step in the effort to develop anti-viral medicine to struggle off infections.
“This paper is about trying to understand the mechanism that makes these RNA escape degradation,” says senior writer Mandy Muller, assistant professor of microbiology. “The next step is to figure out if we can manipulate this to our advantage.”
In the Muller Lab, scholar researchers work with Muller learning how Kaposi sarcoma-related herpesvirus (KSHV) hides for years inside the human physique earlier than looking for to achieve management over human gene expression to finish the viral an infection. At that time, individuals with a weakened immune system might develop Kaposi sarcoma most cancers lesions in the mouth, pores and skin or different organs.
The researchers use genome-large sequencing, publish-transcriptional sequencing and molecular biology to look at how the human cell or the virus is aware of how one can forestall degradation.
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graduate scholar Daniel Macveigh-Fierro
“Viruses are very smart, that’s what I love to say,” Muller says. “They have heaps of methods to stay round, and they don’t do loads of injury for a really very long time, as a result of that’s one solution to cover from the immune system.
“But then, at some point – many, many years later – they reactivate. The way they do this is by triggering a massive RNA degradation event where the virus will wipe out the mRNA from the cell. That means the human system can no longer express the proteins that it needs to express, and that means also that a lot of resources are suddenly available for the virus.”
How and why some RNA are in a position to escape the viral degradation are questions Muller’s group – together with lead writer and graduate scholar Daniel Macveigh-Fierro and co-authors and undergraduates Angelina Cicerchia, Ashley Cadorette and Vasudha Sharma – has been investigating. The analysis was supported by a $1.9 million Maximizing Investigators’ Research Award (MIRA) to Muller in 2020 from the NIH’s National Institute for General Medical Sciences.
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Green dots present protein in chemical modification; cell’s nucleus is blue.
“We show that RNA that escape have a chemical tag on them – a post-transcriptional modification – that makes them different from the others,” Muller explains. “By having this tag, M6A, they can recruit proteins that protect them from degradation.”
Muller has been learning KSHV since she was an undergraduate in her native France, and her mission continues.
“We know you need this protein to protect the RNA from degradation, but we still don’t know how that physically stops the degradation, so that’s what we’re going to look at now,” she says.
Ultimately, understanding the mechanisms and pathways concerned in KSHV an infection might result in the improvement of RNA therapeutics to deal with viral ailments.
“By identifying the determinants of what makes an mRNA either resistant or susceptible to viral-induced decay, we could use those findings to our advantage to better design anti-viral drugs and reshape the outcome of infection,” Muller says.
