A family of putative transcription termination factors shared amongst metazoans and plants

Linder, Tomas; Park, Chan Bae; Asin-Cayuela, Jorge; Pellegrini, Mina; Larsson, Nils‐Göran; Falkenberg, Maria; Samuelsson, Tore; Gustafsson, Claes M.

doi:10.1007/s00294-005-0022-5

Cited by 118 publications

(106 citation statements)

References 27 publications

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“…One, mTERF enhances rRNA transcription by binding 39 to the 16 rRNA gene within the tRNA Leu(UUR) gene and the H1 transcription initiation site . In addition, the most conserved member of the mTERF family, mTERF3, negatively regulates transcription initiation (Linder et al 2005;Park et al 2007).…”

Section: Mtdna Replication and Transcriptionmentioning

confidence: 99%

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The pathophysiology of mitochondrial disease as modeled in the mouse

Wallace¹,

Fan²

2009

Genes Dev.

186

150

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It is now clear that mitochondrial defects are associated with a plethora of clinical phenotypes in man and mouse. This is the result of the mitochondria's central role in energy production, reactive oxygen species (ROS) biology, and apoptosis, and because the mitochondrial genome consists of roughly 1500 genes distributed across the maternal mitochondrial DNA (mtDNA) and the Mendelian nuclear DNA (nDNA). While numerous pathogenic mutations in both mtDNA and nDNA mitochondrial genes have been identified in the past 21 years, the causal role of mitochondrial dysfunction in the common metabolic and degenerative diseases, cancer, and aging is still debated. However, the development of mice harboring mitochondrial gene mutations is permitting demonstration of the direct cause-and-effect relationship between mitochondrial dysfunction and disease. Mutations in nDNA-encoded mitochondrial genes involved in energy metabolism, antioxidant defenses, apoptosis via the mitochondrial permeability transition pore (mtPTP), mitochondrial fusion, and mtDNA biogenesis have already demonstrated the phenotypic importance of mitochondrial defects. These studies are being expanded by the recent development of procedures for introducing mtDNA mutations into the mouse. These studies are providing direct proof that mtDNA mutations are sufficient by themselves to generate major clinical phenotypes. As more different mtDNA types and mtDNA gene mutations are introduced into various mouse nDNA backgrounds, the potential functional role of mtDNA variation in permitting humans and mammals to adapt to different environments and in determining their predisposition to a wide array of diseases should be definitively demonstrated.

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Section: Mtdna Replication and Transcriptionmentioning

confidence: 99%

“…Inactivation of the testis-specific Ant isoform, Ant4 (Linder et al 2005;Rodic et al 2005) caused a severe defect in spermatogenesis (Brower et al 2007). The testes of the Ant4 À/À mice are much smaller than normal, though testicular development is normal until ;17 d after birth.…”

Section: Modification Of Ndna Oxphos Genesmentioning

confidence: 99%

The pathophysiology of mitochondrial disease as modeled in the mouse

Wallace¹,

Fan²

2009

Genes Dev.

186

150

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“…One of these families is the mitochondrial transcription termination factor family (mTERF), members of which have been identified in both metazoans and plants (Linder et al, 2005). The family founder member, human mTERF1, is one of four mammalian mTERF proteins and was identified one-quarter of a century ago as a factor that promotes transcription termination in human mitochondrial extracts (Kruse et al, 1989).…”

mentioning

confidence: 99%

A Member of the Arabidopsis Mitochondrial Transcription Termination Factor Family Is Required for Maturation of Chloroplast Transfer RNA^Ile(GAU)

Romani

Manavski²,

Morosetti

et al. 2015

Plant Physiol.

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Plastid gene expression is crucial for organelle function, but the factors that control it are still largely unclear. Members of the socalled mitochondrial transcription termination factor (mTERF) family are found in metazoans and plants and regulate organellar gene expression at different levels. Arabidopsis (Arabidopsis thaliana) mTERF6 is localized in chloroplasts and mitochondria, and its knockout perturbs plastid development and results in seedling lethality. In the leaky mterf6-1 mutant, a defect in photosynthesis is associated with reduced levels of photosystem subunits, although corresponding messenger RNA levels are unaffected, whereas translational capacity and maturation of chloroplast ribosomal RNAs (rRNAs) are perturbed in mterf6-1 mutants. Bacterial one-hybrid screening, electrophoretic mobility shift assays, and coimmunoprecipitation experiments reveal a specific interaction between mTERF6 and an RNA sequence in the chloroplast isoleucine transfer RNA gene (trnI.2) located in the rRNA operon. In vitro, recombinant mTERF6 bound to its plastid DNA target site can terminate transcription. At present, it is unclear whether disturbed rRNA maturation is a primary or secondary defect. However, it is clear that mTERF6 is required for the maturation of trnI.2. This points to an additional function of mTERFs.

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“…Transcription may also be regulated at the level of termination via the binding of mitochondrial transcription termination factor 1 (MTERF1) to a 28-bp region directly downstream of the two rRNA genes (7,8). MTERF1 belongs to the large MTERF family with many members in metazoans and plants (9). In mammals, a total of four members are known and MTERF1, MTERF2, and MTERF3 have all been suggested to interact with the promoter region and stimulate (10,11) or repress transcription initiation (12).…”

mentioning

confidence: 99%

Structure of the human MTERF4–NSUN4 protein complex that regulates mitochondrial ribosome biogenesis

Spåhr

Habermann

Gustafsson

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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111

102

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Proteins crucial for the respiratory chain are translated by the mitochondrial ribosome. Mitochondrial ribosome biogenesis is therefore critical for oxidative phosphorylation capacity and disturbances are known to cause human disease. This complex process is evolutionary conserved and involves several RNA processing and modification steps required for correct ribosomal RNA maturation. We recently showed that a member of the mitochondrial transcription termination factor (MTERF) family of proteins, MTERF4, recruits NSUN4, a 5-methylcytosine RNA methyltransferase, to the large ribosomal subunit in a process crucial for mitochondrial ribosome biogenesis. Here, we describe the 3D crystal structure of the human MTERF4-NSUN4 complex determined to 2.9 Å resolution. MTERF4 is composed of structurally repeated MTERF-motifs that form a nucleic acid binding domain. NSUN4 lacks an N-or C-terminal extension that is commonly used for RNA recognition by related RNA methyltransferases. Instead, NSUN4 binds to the C-terminus of MTERF4. A positively charged surface forms an RNA binding path from the concave to the convex side of MTERF4 and further along NSUN4 all of the way into the active site. This finding suggests that both subunits of the protein complex likely contribute to RNA recognition. The interface between MTERF4 and NSUN4 contains evolutionarily conserved polar and hydrophobic amino acids, and mutations that change these residues completely disrupt complex formation. This study provides a molecular explanation for MTERF4-dependent recruitment of NSUN4 to ribosomal RNA and suggests a unique mechanism by which other members of the large MTERF-family of proteins can regulate ribosomal biogenesis. mitochondria | translation | X-ray crystallography

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A family of putative transcription termination factors shared amongst metazoans and plants

Cited by 118 publications

References 27 publications

The pathophysiology of mitochondrial disease as modeled in the mouse

The pathophysiology of mitochondrial disease as modeled in the mouse

A Member of the Arabidopsis Mitochondrial Transcription Termination Factor Family Is Required for Maturation of Chloroplast Transfer RNA^Ile(GAU)

Structure of the human MTERF4–NSUN4 protein complex that regulates mitochondrial ribosome biogenesis

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A family of putative transcription termination factors shared amongst metazoans and plants

Cited by 118 publications

References 27 publications

The pathophysiology of mitochondrial disease as modeled in the mouse

The pathophysiology of mitochondrial disease as modeled in the mouse

A Member of the Arabidopsis Mitochondrial Transcription Termination Factor Family Is Required for Maturation of Chloroplast Transfer RNAIle(GAU)

Structure of the human MTERF4–NSUN4 protein complex that regulates mitochondrial ribosome biogenesis

Contact Info

Product

Resources

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A Member of the Arabidopsis Mitochondrial Transcription Termination Factor Family Is Required for Maturation of Chloroplast Transfer RNA^Ile(GAU)