Research in the Patel Lab focuses on the mechanisms of biological processes such as (i) mitochondrial DNA replication, (ii) mitochondrial gene expression, and (iii) viral RNA sensing by the innate immune receptors.
We employ a combination of biochemical, molecular, cell, and structural biology approaches to elucidate the molecular mechanisms and regulation in these processes. Ensemble and single molecule methods characterize protein-nucleic acid interactions, DNA and RNA synthesis, and CryoEM methods provide high-resolution molecular structures.
Current projects:
(i) Structural and mechanistic studies of the human mitochondrial RNA polymerase (POLRMT) and its regulation by the initiation (TFB2M and TFAM) and elongation (TEFM) transcription factors.
(ii) Reconstitution of the human mitochondrial replisome (polymerase gamma, Twinkle helicase, and SSB) and studying the effects of disease mutants of Twinkle on replication activities.
(iii) Self and nonself discrimination by the RIG-I family viral RNA sensors and their regulation by the LGP2 protein.
We employ a combination of biochemical, molecular, cell, and structural biology approaches to elucidate the molecular mechanisms and regulation in these processes. Ensemble and single molecule methods characterize protein-nucleic acid interactions, DNA and RNA synthesis, and CryoEM methods provide high-resolution molecular structures.
Current projects:
(i) Structural and mechanistic studies of the human mitochondrial RNA polymerase (POLRMT) and its regulation by the initiation (TFB2M and TFAM) and elongation (TEFM) transcription factors.
(ii) Reconstitution of the human mitochondrial replisome (polymerase gamma, Twinkle helicase, and SSB) and studying the effects of disease mutants of Twinkle on replication activities.
(iii) Self and nonself discrimination by the RIG-I family viral RNA sensors and their regulation by the LGP2 protein.
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The cryo-EM structures captured the yeast mitochondrial RNA polymerase and its transcription factor, catalyzing a de novo transcription initiation reaction to synthesize an 8-nt long RNA transcript before transitioning to the elongation complex.
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The movie shows the multidomain RIG-I protein capturing the viral RNA and undergoing conformational changes to expose the signaling domains for downstream signal transduction and immune activation.
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