Sunday 7 March 2021
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Princeton - 13 days ago

Rising Stars Seminar Series: The mitochondrial genome as a transcriptional condensate

Mitochondria contain an autonomous and spatially segregated genome. The organizational unit of their genome is the nucleoid, which consists of mitochondrial DNA (mtDNA) and associated architectural proteins. We have recently found that phase separation is the primary physical mechanism for assembly and size-control of the mitochondrial nucleoid. The major mtDNA-binding protein TFAM spontaneously phase separates in vitro via weak, multivalent interactions into droplets with slow internal dynamics. The mitochondrial transcriptional components, including mtDNA, the polymerase POLRMT, and transcription factor TFB2M, further partition with TFAM into heterogenous, viscoelastic droplets in vitro, which recapitulate the dynamics and behavior of mt-nucleoids in vivo. We are currently assessing the effect of condensate formation on transcription kinetics and mt-nucleoid morphology. Our results point to phase separation as an evolutionarily conserved mechanism of genome organization and function.


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