TEFM regulates both transcription elongation and RNA processing in mitochondria

Shan Jiang, Camilla Koolmeister, Jelena Misic, Stefan Siira, Inge Kühl, Eduardo Silva Ramos, Maria Miranda, Min Jiang, Viktor Posse, Oleksandr Lytovchenko, Ilian Atanassov, Florian A. Schober, Rolf Wibom, Kjell Hultenby, Dusanka Milenkovic, Claes M. Gustafsson, Aleksandra Filipovska, Nils Göran Larsson

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4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere48101
Number of pages18
JournalEMBO Reports
Volume20
Issue number6
DOIs
Publication statusPublished - 1 Jun 2019

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    Jiang, S., Koolmeister, C., Misic, J., Siira, S., Kühl, I., Silva Ramos, E., Miranda, M., Jiang, M., Posse, V., Lytovchenko, O., Atanassov, I., Schober, F. A., Wibom, R., Hultenby, K., Milenkovic, D., Gustafsson, C. M., Filipovska, A., & Larsson, N. G. (2019). TEFM regulates both transcription elongation and RNA processing in mitochondria. EMBO Reports, 20(6), [e48101]. https://doi.org/10.15252/embr.201948101