TEFM regulates both transcription elongation and RNA processing in mitochondria

被引：65

作者：

Jiang, Shan ^{[1
,2
]}

Koolmeister, Camilla ^{[1
,2
]}

Misic, Jelena ^{[1
,2
]}

Siira, Stefan ^{[3
,4
]}

Kuehl, Inge ^{[5
,6
]}

Ramos, Eduardo Silva ^{[5
]}

Miranda, Maria ^{[5
]}

Jiang, Min ^{[5
]}

Posse, Viktor ^{[7
]}

Lytovchenko, Oleksandr ^{[1
,2
]}

Atanassov, Ilian ^{[8
]}

Schober, Florian A. ^{[2
,9
]}

Wibom, Rolf ^{[1
,10
]}

Hultenby, Kjell ^{[11
]}

Milenkovic, Dusanka ^{[5
]}

Gustafsson, Claes M. ^{[7
]}

Filipovska, Aleksandra ^{[3
,4
]}

Larsson, Nils-Goeran ^{[1
,2
,5
,10
]}

机构：

[1] Karolinska Inst, Dept Med Biochem & Biophys, Stockholm, Sweden

[2] Karolinska Inst, Max Planck Inst Biol Ageing, Karolinska Inst Lab, Stockholm, Sweden

[3] Univ Western Australia, Harry Perkins Inst Med Res, Perth, WA, Australia

[4] Univ Western Australia, Ctr Med Res, Perth, WA, Australia

[5] Max Planck Inst Biol Ageing, Dept Mitochondria Biol, Cologne, Germany

[6] Univ Paris Saclay, Univ Paris Sud, Inst Integrat Biol Cell, CEA,CNRS,UMR 9198, Gif Sur Yvette, France

[7] Univ Gothenburg, Dept Med Biochem & Cell Biol, Gothenburg, Sweden

[8] Max Planck Inst Biol Ageing, Prote Core Facil, Cologne, Germany

[9] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden

[10] Karolinska Univ Hosp, Ctr Inherited Metab Dis, Stockholm, Sweden

[11] Karolinska Inst, Div Clin Res Ctr, Dept Lab Med, Stockholm, Sweden

来源：

EMBO REPORTS | 2019年 / 20卷 / 06期

基金：

瑞典研究理事会; 英国医学研究理事会; 澳大利亚研究理事会;

关键词：

mtDNA replication; RNA processing; transcription elongation; RIBOSOMAL-PROTEIN L12; DNA-REPLICATION; GRANULES; POLYMERASE; STABILITY; HYBRID; SITE; IDENTIFICATION; TRANSLATION; MAINTENANCE;

D O I：

10.15252/embr.201948101

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Regulation of replication and expression of mitochondrial DNA (mtDNA) is essential for cellular energy conversion via oxidative phosphorylation. The mitochondrial transcription elongation factor (TEFM) has been proposed to regulate the switch between transcription termination for replication primer formation and processive, near genome-length transcription for mtDNA gene expression. Here, we report that Tefm is essential for mouse embryogenesis and that levels of promoter-distal mitochondrial transcripts are drastically reduced in conditional Tefm-knockout hearts. In contrast, the promoter-proximal transcripts are much increased in Tefm knockout mice, but they mostly terminate before the region where the switch from transcription to replication occurs, and consequently, de novo mtDNA replication is profoundly reduced. Unexpectedly, deep sequencing of RNA from Tefm knockouts revealed accumulation of unprocessed transcripts in addition to defective transcription elongation. Furthermore, a proximity-labeling (BioID) assay showed that TEFM interacts with multiple RNA processing factors. Our data demonstrate that TEFM acts as a general transcription elongation factor, necessary for both gene transcription and replication primer formation, and loss of TEFM affects RNA processing in mammalian mitochondria.

引用

页数：18

共 82 条

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