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Albany 2013: Book of Abstracts

category image Albany 2013
Conversation 18
June 11-15 2013
©Adenine Press (2012)

Put a stop to it: termination of mitochondrial transcription

Deficiencies in mitochondrial protein production are associated with human disease and aging. Given the central role of transcription in gene expression, recent years have seen a renewed interest in understanding the molecular mechanisms controlling this process. Mterf proteins have been implicated in modulating transcription, replication and protein synthesis. We have solved the structure of a member of this family, the human mitochondrial transcriptional terminator MTERF1, bound to dsDNA containing the termination sequence. The structure indicates that upon sequence recognition MTERF1 unwinds the DNA molecule, promoting eversion of three nucleotides. Base flipping is critical for stable binding and transcriptional termination. Additional structural and biochemical results provide insight into the DNA binding mechanism and explain how MTERF1 recognizes its target sequence. Furthermore, the identification of termination defects resulting from a number of mtDNA mutations has led to the suggestion that this could be a common mechanism influencing pathogenesis in a number of mitochondrial diseases, highlighting the importance of understanding the processes that regulate transcription in human mitochondria. Our results provide insight into the role of mterf proteins and suggest a link between mitochondrial disease and the regulation of mitochondrial transcription.

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This research has been supported by NIH R00 CS015421.

References

    Yakubovskaya E, Mejia E, Byrnes J, Hambardjieva E, Garcia-Diaz M ( 2010) Helix unwinding and base flipping enable human MTERF1 to terminate mitochondrial transcription. Cell 141(6), 982-993.

    Jiménez-Menéndez N, Fernández-Millán P, Rubio-Cosials A, Arnan C, Montoya J, Jacobs HT, Bernadó P, Coll M, Usón I, Solà M. (2010) Human mitochondrial mTERF wraps around DNA through a left-handed superhelical tandem repeat. Nat Struct Mol Biol. 17(7), 891-893.


Yakubovskaya E
Mejia E
Byrnes J
Hambardjieva E
Garcia-Diaz M.

Department of Pharmacological Sciences
Stony Brook University
Stony Brook, NY 11794, USA.

Ph: (631) 444-4169
Fx: (631) 444-3218
elena@pharm.stonybrook.edu