The Role of MTERF-3 in Mitochondrial Transcription

Subject Area

Biochemistry and Molecular Biology

Description

The Mitochondrial Termination Factor (MTERF) family is a protein group of mitochondrial termination factors that are classified as regulators. Each MTERF protein has their own specialized role with respect to mitochondrial transcription, and not all are terminator factors. The protein group is based on sequence similarly, and the MTERF-3 protein is the most conserved of the family showing a crucial role across species. This is supported by the knockout mice exhibiting embryonic lethality when the gene is removed. Understanding the regulatory role of MTERF-3 and its interactions with the mitochondrial transcription machinery is the major aim of this project. To analyze MTERF-3 interactions molecularly, DNA-binding and protein-protein interactions will be assessed. The mitochondrial core transcription proteins are the mitochondrial RNA polymerase (POLRMT), mitochondrial transcription factor A (TFAM), and mitochondrial transcription factor B2 (TFB2M). These proteins exhibit key functions in transcription and have previously noted interactions with MTERF proteins to regulate gene expression. For these assays, MTERF-3 was cloned and the protein expressed and purified. To examine the protein-protein interactions, functional assays including POLRMT, TFAM, and TFB2M, and in vitro transcription will be performed to analyze the role of MTERF-3 in mitochondrial transcription. By understanding the MTERF-3 role in mitochondria, we can better understand its role within disease.

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The Role of MTERF-3 in Mitochondrial Transcription

The Mitochondrial Termination Factor (MTERF) family is a protein group of mitochondrial termination factors that are classified as regulators. Each MTERF protein has their own specialized role with respect to mitochondrial transcription, and not all are terminator factors. The protein group is based on sequence similarly, and the MTERF-3 protein is the most conserved of the family showing a crucial role across species. This is supported by the knockout mice exhibiting embryonic lethality when the gene is removed. Understanding the regulatory role of MTERF-3 and its interactions with the mitochondrial transcription machinery is the major aim of this project. To analyze MTERF-3 interactions molecularly, DNA-binding and protein-protein interactions will be assessed. The mitochondrial core transcription proteins are the mitochondrial RNA polymerase (POLRMT), mitochondrial transcription factor A (TFAM), and mitochondrial transcription factor B2 (TFB2M). These proteins exhibit key functions in transcription and have previously noted interactions with MTERF proteins to regulate gene expression. For these assays, MTERF-3 was cloned and the protein expressed and purified. To examine the protein-protein interactions, functional assays including POLRMT, TFAM, and TFB2M, and in vitro transcription will be performed to analyze the role of MTERF-3 in mitochondrial transcription. By understanding the MTERF-3 role in mitochondria, we can better understand its role within disease.