Mount Sinai Researchers Develop Tool to Determine Function of MicroRNAs

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As microRNA biology has been implicated in everything from the development of cancer to virus infections, a new tool developed by scientists at the Icahn School of Medicine at Mount Sinai holds tremendous potential to develop new therapies that involve these small regulatory fragments of RNA.

As microRNA biology has been implicated in everything from the development of cancer to virus infections, a new tool developed by scientists at the Icahn School of Medicine at Mount Sinai holds tremendous potential to develop new therapies that involve these small regulatory fragments of RNA. The scientists’ findings are detailed in a study, titled “MicroRNA Function is Limited to Cytokine Control in the Acute Response to Virus Infection,” published in the December issue of Cell Host & Microbe. While the article focuses on microRNA function as it pertains to virus infection, the development and characterization of this new tool has implications that far exceed the field of microbiology.

“Apart from their roles in causing medical maladies, viruses have long been used as tools to reveal unappreciated aspects of biology, providing us with insights into the many unknowns of how our cells function,” said Benjamin tenOever, PhD, Fishberg Professor of Microbiology at the Icahn School of Medicine at Mount Sinai and corresponding author of the study. “We developed a tool based on a poxvirus gene that allows us to manipulate microRNA populations in any tissue or cell type we desire”.

With the capacity to fine-tune protein expression, microRNAs, also called miRNAs, help regulate cell maintenance and differentiation. This regulatory pathway is known to often malfunction in the development of cancer and its role in the response to virus infection has remained largely unknown and difficult to study. To determine the global role of miRNAs in both cell biology and the response to virus infection, the team at Mount Sinai, led by Dr. tenOever and PhD candidate Lauren C. Aguado, designed and generated a synthetic vector that rapidly eliminates total cellular miRNA populations in any cell or tissue to which it was administered.

While loss of miRNAs had a negligible impact on the cell’s immediate reaction to virus or the short term biology of the cell, sustained depletion was found to have dramatic results on gene expression that was coupled to a burst of cytokines – protein messengers that alert the immune system of a problem. In all, this work concludes that miRNA function is limited to modulating the biology of the cell over long periods of time. Having a tool that can now manipulate these responses provides us with an unprecedented platform to reprogram healthy cells or treat diseases such as cancer where these pathways have malfunctioned.

About the Mount Sinai Health System
The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services — from community-based facilities to tertiary and quaternary care.

The System includes approximately 6,100 primary and specialty care physicians; 12 minority-owned free-standing ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. Physicians are affiliated with the renowned Icahn School of Medicine at Mount Sinai, which is ranked among the highest in the nation in National Institutes of Health funding per investigator. The Mount Sinai Hospital is ranked as one of the nation’s top 10 hospitals in Geriatrics, Cardiology/Heart Surgery, and Gastroenterology, and is in the top 25 in five other specialties in the 2015-2016 “Best Hospitals” issue of U.S. News & World Report. Mount Sinai’s Kravis Children’s Hospital also is ranked in seven out of ten pediatric specialties by U.S. News & World Report. The New York Eye and Ear Infirmary of Mount Sinai is ranked 11th nationally for Ophthalmology, while Mount Sinai Beth Israel is ranked regionally.

For more information, visit http://www.mountsinaihealth.org/ or find Mount Sinai on Facebook, Twitter and YouTube.
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Sid Dinsay
Mount Sinai Health System
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