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[Preprint]. 2024 Jun 10:2024.03.28.587146. [Version 2] doi: 10.1101/2024.03.28.587146

Figure 4. Antiviral signaling is amplified via the MDA5-mtRNA-SLIRP positive feedback loop.

Figure 4.

(A) Cytosolic mtRNA expression in poly I:C transfected cells with or without SLIRP (n=4). (B, C) The effect of BAK1 downregulation on the ISG (B) and mtRNA (C) induction by poly I:C. (D) Analysis of mtRNA expression upon poly I:C transfection with or without MDA5. (E) The mtRNA expression upon IFN-β treatment. (F) Western blot analysis for SLIRP localization upon poly I:C with or without MDA5. JNK is used as a marker for the cytosol fraction while AIF is used as a marker for the membrane fraction. (G, H) The expression of MDA5 mRNA (G) and protein (H) expression after poly I:C transfection in cells deficient in SLIRP. (I) The effect of SLIRP downregulation on the IRF3 phosphorylation upon poly I:C. (J) A model for the positive feedback amplification of antiviral signaling consists of mtRNA induction, cytosolic release, and MDA5 activation. Unless mentioned, three independent experiments were carried out, and error bars denote s.e.m. All of the statistical significances were calculated using one-tail Student’s t-tests; * p ≤ 0.05, ** p ≤ 0.01, and *** p ≤ 0.001.