Human mitochondrial RNA polymerase: Structure-function, mechanism and inhibition

Jamie Jon Arnold, Eric D. Smidansky, Ibrahim Moustafa, Craig Eugene Cameron

Research output: Contribution to journalReview article

26 Citations (Scopus)

Abstract

Transcription of the human mitochondrial genome is required for the expression of 13 subunits of the respiratory chain complexes involved in oxidative phosphorylation, which is responsible for meeting the cells' energy demands in the form of ATP. Also transcribed are the two rRNAs and 22 tRNAs required for mitochondrial translation. This process is accomplished, with the help of several accessory proteins, by the human mitochondrial RNA polymerase (POLRMT, also known as h-mtRNAP), a nuclear-encoded single-subunit DNA-dependent RNA polymerase (DdRp or RNAP) that is distantly related to the bacteriophage T7 class of single-subunit RNAPs. In addition to its role in transcription, POLRMT serves as the primase for mitochondrial DNA replication. Therefore, this enzyme is of fundamental importance for both expression and replication of the human mitochondrial genome. Over the past several years rapid progress has occurred in understanding POLRMT and elucidating the molecular mechanisms of mitochondrial transcription. Important accomplishments include development of recombinant systems that reconstitute human mitochondrial transcription in vitro, determination of the X-ray crystal structure of POLRMT, identification of distinct mechanisms for promoter recognition and transcription initiation, elucidation of the kinetic mechanism for POLRMT-catalyzed nucleotide incorporation and discovery of unique mechanisms of mitochondrial transcription inhibition including the realization that POLRMT is an off target for antiviral ribonucleoside analogs. This review summarizes the current understanding of POLRMT structure-function, mechanism and inhibition. This article is part of a Special Issue entitled: Mitochondrial Gene Expression.

Original languageEnglish (US)
Pages (from-to)948-960
Number of pages13
JournalBiochimica et Biophysica Acta - Gene Regulatory Mechanisms
Volume1819
Issue number9-10
DOIs
StatePublished - Sep 1 2012

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Mitochondrial Genome
Human Genome
DNA-Directed RNA Polymerases
Transcription
DNA Primase
Ribonucleosides
Bacteriophage T7
Mitochondrial Genes
Oxidative Phosphorylation
Electron Transport
Transfer RNA
DNA Replication
Mitochondrial DNA
Antiviral Agents
Nucleotides
Adenosine Triphosphate
X-Rays
Gene Expression
Enzymes
Genes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Arnold, Jamie Jon ; Smidansky, Eric D. ; Moustafa, Ibrahim ; Cameron, Craig Eugene. / Human mitochondrial RNA polymerase : Structure-function, mechanism and inhibition. In: Biochimica et Biophysica Acta - Gene Regulatory Mechanisms. 2012 ; Vol. 1819, No. 9-10. pp. 948-960.
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Human mitochondrial RNA polymerase : Structure-function, mechanism and inhibition. / Arnold, Jamie Jon; Smidansky, Eric D.; Moustafa, Ibrahim; Cameron, Craig Eugene.

In: Biochimica et Biophysica Acta - Gene Regulatory Mechanisms, Vol. 1819, No. 9-10, 01.09.2012, p. 948-960.

Research output: Contribution to journalReview article

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