Evidence map›Paper›PMID 36629253›Full record

ArticleNucleic acids research2023

Translation initiation of leaderless and polycistronic transcripts in mammalian mitochondria.

Cristina Remes, Anas Khawaja, Sarah F Pearce, Adam M Dinan, Shreekara Gopalakrishna, Miriam Cipullo, Vasileios Kyriakidis, Jingdian Zhang, Xaquin Castro Dopico, Olessya Yukhnovets and 4 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
5.4field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 35 citations in OpenAlex.

  1. Article
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  6. Transplantation ofMicrobiology (Reading, England) · 2026
    Article
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  8. Article
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  13. Article
  14. Central dogma rates in human mitochondria.Human molecular genetics · 2024
    Review
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  18. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 6 institutions in 5 countries.

Cristina RemesDepartment of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA.
Anas KhawajaDepartment of Medical Biochemistry and Biophysics, Division of Molecular Metabolism, Karolinska Institutet, Stockholm 17165, Sweden.
Sarah F PearceDepartment of Medical Biochemistry and Biophysics, Division of Molecular Metabolism, Karolinska Institutet, Stockholm 17165, Sweden.
Adam M DinanDepartment of Pathology, University of Cambridge, Cambridge, UK.
Shreekara GopalakrishnaDepartment of Medical Biochemistry and Biophysics, Division of Molecular Metabolism, Karolinska Institutet, Stockholm 17165, Sweden.ORCID 0000-0002-8555-0292
Miriam CipulloDepartment of Medical Biochemistry and Biophysics, Division of Molecular Metabolism, Karolinska Institutet, Stockholm 17165, Sweden.
Vasileios KyriakidisDepartment of Medical Biochemistry and Biophysics, Division of Molecular Metabolism, Karolinska Institutet, Stockholm 17165, Sweden.
Jingdian ZhangDepartment of Medical Biochemistry and Biophysics, Division of Molecular Metabolism, Karolinska Institutet, Stockholm 17165, Sweden.
Xaquin Castro DopicoDepartment of Microbiology, Tumor & Cell Biology, Karolinska Institutet, Stockholm 171 77, Sweden.
Olessya YukhnovetsRWTH Aachen, I. Physikalisches Institut (IA), Aachen, Germany.
Ilian AtanassovProteomics Core Facility, Max-Planck-Institute for Biology of Ageing, Joseph-Stelzmann-Str. 9b, 50931 Cologne, Germany.ORCID 0000-0001-8259-2545
Andrew E FirthDepartment of Pathology, University of Cambridge, Cambridge, UK.
Barry CoopermanDepartment of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA.
Joanna RorbachDepartment of Medical Biochemistry and Biophysics, Division of Molecular Metabolism, Karolinska Institutet, Stockholm 17165, Sweden.ORCID 0000-0002-2891-2840
Karolinska Institutet · SEUniversity of Cambridge · GBUniversity of Pennsylvania · USForschungszentrum Jülich · DEMax Planck Institute for Biology of Ageing · DEStellenbosch University · ZA

Funding

Mechanisms of Induced Nonsense Suppression and MisreadingR01GM127374 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI BARRY S. COOPERMAN · 2018 to 2026
$2.3M
European Research Council 646891NIGMS NIH HHS R01 GM127374Wellcome Trust 106207
6 · The paper itself

Abstract

The synthesis of mitochondrial OXPHOS complexes is central to cellular metabolism, yet many molecular details of mitochondrial translation remain elusive. It has been commonly held view that translation initiation in human mitochondria proceeded in a manner similar to bacterial systems, with the mitoribosomal small subunit bound to the initiation factors, mtIF2 and mtIF3, along with initiator tRNA and an mRNA. However, unlike in bacteria, most human mitochondrial mRNAs lack 5' leader sequences that can mediate small subunit binding, raising the question of how leaderless mRNAs are recognized by mitoribosomes. By using novel in vitro mitochondrial translation initiation assays, alongside biochemical and genetic characterization of cellular knockouts of mitochondrial translation factors, we describe unique features of translation initiation in human mitochondria. We show that in vitro, leaderless mRNA transcripts can be loaded directly onto assembled 55S mitoribosomes, but not onto the mitoribosomal small subunit (28S), in a manner that requires initiator fMet-tRNAMet binding. In addition, we demonstrate that in human cells and in vitro, mtIF3 activity is not required for translation of leaderless mitochondrial transcripts but is essential for translation of ATP6 in the case of the bicistronic ATP8/ATP6 transcript. Furthermore, we show that mtIF2 is indispensable for mitochondrial protein synthesis. Our results demonstrate an important evolutionary divergence of the mitochondrial translation system and further our fundamental understanding of a process central to eukaryotic metabolism.

Indexed as

MitochondriaPeptide Chain Initiation, TranslationalAnimalsBacteriaHumansMammalsMitochondrial ProteinsPeptide Initiation FactorsRNA, MessengerMitochondrial ProteinsPeptide Initiation FactorsRNA, Messenger

Identifiers

PMID36629253
PMCPMC9881170
OpenAlexW4315620059

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.