Evidence map›Paper›PMID 32324744›Full record

ArticlePLoS genetics2020

Targeting mitochondrial and cytosolic substrates of TRIT1 isopentenyltransferase: Specificity determinants and tRNA-i6A37 profiles.

Abdul Khalique, Sandy Mattijssen, Alexander F Haddad, Shereen Chaudhry, Richard J Maraia

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.0field-weighted citation impact, top 26% 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

13 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Article
  3. [Abnormal transfer RNA epigenetic modifications and related impact on neurodegenerative diseases].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024
    Review
  4. Article
  5. Review
  6. Review
  7. Review
  8. ExtracellularRNA (New York, N.Y.) · 2022
    Article
  9. Article
  10. Review
  11. Review
  12. Failure to Guard: Mitochondrial Protein Quality Control in Cancer.International journal of molecular sciences · 2021
    Review
  13. Article
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

5 authors at 1 institution in 1 country.

Abdul KhaliqueIntramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, of the National Institutes of Health, Bethesda, Maryland, United States of America.
Sandy MattijssenIntramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, of the National Institutes of Health, Bethesda, Maryland, United States of America.ORCID 0000-0002-4285-7438
Alexander F HaddadIntramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, of the National Institutes of Health, Bethesda, Maryland, United States of America.
Shereen ChaudhryIntramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, of the National Institutes of Health, Bethesda, Maryland, United States of America.ORCID 0000-0002-3820-4573
Richard J MaraiaIntramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, of the National Institutes of Health, Bethesda, Maryland, United States of America.ORCID 0000-0002-5209-0066
National Institutes of Health · US

Funding

Molecular Regulation Of RNA MetabolismZIAHD000412 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI MARAIA, RICHARD J · 2009 to 2025
$31.6M
MOLECULAR REGULATION OF GENE EXPRESSIONZ01HD000412 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI MARAIA, RICHARD J · 1988 to 2008
$1.8M
Intramural NIH HHS Z01 HD000412Wellcome Trust
6 · The paper itself

Abstract

The tRNA isopentenyltransferases (IPTases), which add an isopentenyl group to N6 of A37 (i6A37) of certain tRNAs, are among a minority of enzymes that modify cytosolic and mitochondrial tRNAs. Pathogenic mutations to the human IPTase, TRIT1, that decrease i6A37 levels, cause mitochondrial insufficiency that leads to neurodevelopmental disease. We show that TRIT1 encodes an amino-terminal mitochondrial targeting sequence (MTS) that directs mitochondrial import and modification of mitochondrial-tRNAs. Full understanding of IPTase function must consider the tRNAs selected for modification, which vary among species, and in their cytosol and mitochondria. Selection is principally via recognition of the tRNA A36-A37-A38 sequence. An exception is unmodified tRNATrpCCA-A37-A38 in Saccharomyces cerevisiae, whereas tRNATrpCCA is readily modified in Schizosaccharomyces pombe, indicating variable IPTase recognition systems and suggesting that additional exceptions may account for some of the tRNA-i6A37 paucity in higher eukaryotes. Yet TRIT1 had not been characterized for restrictive type substrate-specific recognition. We used i6A37-dependent tRNA-mediated suppression and i6A37-sensitive northern blotting to examine IPTase activities in S. pombe and S. cerevisiae lacking endogenous IPTases on a diversity of tRNA-A36-A37-A38 substrates. Point mutations to the TRIT1 MTS that decrease human mitochondrial import, decrease modification of mitochondrial but not cytosolic tRNAs in both yeasts. TRIT1 exhibits clear substrate-specific restriction against a cytosolic-tRNATrpCCA-A37-A38. Additional data suggest that position 32 of tRNATrpCCA is a conditional determinant for substrate-specific i6A37 modification by the restrictive IPTases, Mod5 and TRIT1. The cumulative biochemical and phylogenetic sequence analyses provide new insights into IPTase activities and determinants of tRNA-i6A37 profiles in cytosol and mitochondria.

Indexed as

Alkyl and Aryl TransferasesAllelesAnticodonCytosolGenetic Complementation TestHumansMitochondriaMutationRNA, TransferSaccharomyces cerevisiaeSchizosaccharomycesSequence AlignmentSubstrate SpecificityAlkyl and Aryl TransferasesAnticodonRNA, TransferTRIT1 protein, human

Identifiers

PMID32324744
PMCPMC7200024
OpenAlexW3017426991

What OpenQuestion holds

Textmetadata
LicenceCC0
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.