New life sciences study findings have been published by scientists at Kyoto University
2009 JUL 13 - (NewsRx.com) -- According to recent research from Kyoto, Japan, "Retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) are essential for detecting viral RNA and triggering antiviral responses, including production of type I interferon. We analyzed the phenotype of non-synonymous mutants of human RIG-I and MDA5 reported in databases by functional complementation in cell cultures." "Of seven missense mutations of RIG-I, S183I, which occurs within the second caspase recruitment domain repeat, inactivated this domain and conferred a dominant inhibitory function. Of 10 mutants of MDA5, two exhibited loss of function. A nonsense mutation, E627*, resulted in deletion of the C-terminal region and double-stranded RNA (dsRNA) binding activity. Another loss of function mutation, I923V, which occurs within the C-terminal domain, did not affect dsRNA binding activity, suggesting a novel and essential role for this residue in the signaling. Remarkably, these mutations are implicated in resistance to type I diabetes. However, the A946T mutation of MDA5, which has been implicated in type I diabetes by previous genetic analyses, affected neither dsRNA binding nor IFN gene activation," wrote T. Shigemoto and colleagues, Kyoto University. The researchers concluded: "These results provide new insights into the structure-function relationship of RIG-I-like receptors as well as into human RIG-I-like receptor polymorphisms, antiviral innate immunity, and autoimmune diseases." Shigemoto and colleagues published their study in the Journal of Biological Chemistry (Identification of Loss of Function Mutations in Human Genes Encoding RIG-I and MDA5 IMPLICATIONS FOR RESISTANCE TO TYPE I DIABETES. Journal of Biological Chemistry, 2009;284(20):13348-13354). For additional information, contact T. Fujita, Kyoto University, Molecular Genetics Laboratory, Institute Virus Research, Kyoto 6068507, Japan. Publisher contact information for the Journal of Biological Chemistry is: American Society Biochemistry Molecular Biology Inc., 9650 Rockville Pike, Bethesda, MD 20814-3996, USA. Keywords: Japan, Kyoto, Life Sciences, Type 1 Diabetes, Insulin Dependent Diabetes Mellitus, Melanoma, Virology, Viral Therapy, Treatment, Viral Inhibition, Antiviral, Virus, Enzyme Research, Caspase, Interferon, Biological Chemistry, Kyoto University. This article was prepared by Diabetes Week editors from staff and other reports. Copyright 2009, Diabetes Week via NewsRx.com.
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