A chemical modification of RNA that can be influenced by diet appears to play a key role in autosomal dominant polycystic kidney disease (ADPKD), an inherited disorder that is the fourth leading cause of kidney failure in the U.S., University of Texas Southwestern (UTSW) researchers report in a new study. The findings, published online on April 13, 2021 in Cell Metabolism, suggest possible new ways to treat this incurable condition. The article is titled “A Methionine-Mettl3-N6-Methyladenosine Axis Promotes Polycystic Kidney Disease” (https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00131-5). Approximately 600,000 Americans and 12.5 million people worldwide have ADPKD, a condition caused by mutations in either of two genes, PKD1 or PKD2. These mutations cause kidney tubules (small tubes that filter blood and generate urine) to dilate, forming cysts that grossly enlarge the kidneys. In approximately 50 percent of patients, these cysts eventually cause kidney failure, necessitating dialysis or a kidney transplant. (Image at left shows enormous polycystic kidney versus normal kidney). Although one FDA-approved drug exists to treat ADPKD, it merely slows the decline in kidney function, explain study leaders Vishal Patel, MD, Associate Professor of Internal Medicine at UTSW, and Harini Ramalingam, PhD, a postdoctoral fellow in Dr. Patel's lab. More treatments for this condition are urgently needed, they say, but the molecular mechanisms that cause ADPKD to develop and progress are still not fully known. To better understand this condition, Dr. Patel, Dr. Ramalingam, and their colleagues investigated whether chemical modifications to the genetic molecule RNA, which translates instructions from DNA to produce proteins in the body, could play a part.
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