Activation of type 1 interferon response is extensively connected with the antiviral immunity and pathogenesis of autoimmune diseases. Here, we found that IRGM, whose deficiency is linked with the genesis of several autoimmune disorders, is a master negative regulator of the interferon response. Mechanistically, we show that IRGM interacts with nucleic acid sensor proteins, including cGAS and RIG-I, and mediates their autophagic degradation to restrain activation of interferon signaling. Further, IRGM maintains mitophagy flux, and its deficiency results in the accumulation of defunct leaky mitochondria that releases cytosolic DAMPs triggering activation of interferon responses via cGAS-STING and RIG-I-MAVS signaling axis. Due to an enduring type 1 IFN response in IRGM-deficient cells and mice, they were intrinsically resistant to infection of the Japanese Encephalitis virus, Herpes Simplex virus, and Chikungunya virus. Altogether, this study defines the molecular mechanisms by which IRGM maintains interferon homeostasis and protects from autoimmune diseases. Further, it identifies IRGM as a broad therapeutic target for defense against viruses.
Swarna (MTU7029), an Indian mega-variety of rice, is cultivated on an estimated 8Mha of land. There is a pressing need to address yield stagnation and wider adaptability to irrigated lowland and rainfed ecologies as a result of the negative consequences of climate change and population growth. The present study was aimed at improving Swarna for two yield-related traits through marker-assisted backcross breeding strategy by introgression of OsSPL14 (panicle branching) and SCM2 (stronger culm). Foreground and background selection was carried out at each generation. Homozygous BC2F2 plants harbouring both yield-enhancing genes were identified and advanced through pedigree selection till BC2F5 and evaluated in station trials. Three promising lines possessing higher yield over recurrent parent were identified, and a single line, IET 27661 exhibited superior yield in multi-location trials of the All India Coordinated Rice Improvement Programme (AICRIP) and was found to be promising.
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