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Mount Sinai Study Reveals Significant Differences in RNA Editing Between Postmortem and Living Human Brain

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Researchers from the Icahn School of Medicine at Mount Sinai have shed valuable light on the nuanced functions and intricate regulatory methods of RNA editing, a critical mechanism underlying brain development and disease.

In a study published June 26 in Nature Communications, the team reported finding major differences between postmortem and living prefrontal cortex brain tissues as they relate to one of the most abundant RNA modifications in the brain, known as adenosine-to-inosine (A-to-I) editing. This discovery will play a significant role in shaping the development of diagnostics and therapies for brain diseases.

To investigate, the research team anchored their study around the Living Brain Project, in which dorsolateral prefrontal cortex (DLPFC) tissues from living people are obtained during neurosurgical procedures for deep brain stimulation, an elective treatment for neurological illness. For comparison, a cohort of postmortem DLPFC tissues across three brain banks was assembled to match the living cohort for key demographic and clinical variables. The team investigated multiple genomic data types from the Living Brain Project, including bulk tissue RNA sampling, single-nuclei RNA sequencing, and whole-genome sequencing. The generation of this data is being described in multiple forthcoming Living Brain Project manuscripts.

Michael S. Breen, PhD
Assistant Professor of Psychiatry, Genetics and Genomic Sciences
Faculty of Icahn Genomics Institute, the Seaver Autism Center for Research and Treatment, the Friedman Brain Insitute, and the Mindich Child Health and Development Institute
Icahn School of Medicine at Mount Sinai

Alexander Charney, MD, PhD
Associate Professor, Departments of Psychiatry and Genetics & Genomic Sciences
Departments of Neuroscience and Neurosurgery
Director of the Charles Bronfman Institute for Personalized Medicine
Icahn School of Medicine at Mount Sinai

Brian Kopell, MD
Associate Professor, Departments of Psychiatry and Genetics & Genomic Sciences
Departments of Neuroscience and Neurosurgery
Director of the Charles Bronfman Institute for Personalized Medicine
Icahn School of Medicine at Mount Sinai

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