Evidence map›Paper›PMID 29034140›Full record

ArticleTranslation (Austin, Tex.)2017

Regulation of gene expression by translation factor eIF5A: Hypusine-modified eIF5A enhances nonsense-mediated mRNA decay in human cells.

Mainul Hoque, Ji Yeon Park, Yun-Juan Chang, Augusto D Luchessi, Tavane D Cambiaghi, Raghavendra Shamanna, Hartmut M Hanauske-Abel, Bart Holland, Tsafi Pe'ery, Bin Tian and 1 more

Open access · diamondAbstract read
In one paragraph

Article in Translation (Austin, Tex.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
0.9field-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

17 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Article
  3. Polyamines and hypusination are important forInfection and immunity · 2023
    Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Nonsense-Mediated mRNA Decay Begins Where Translation Ends.Cold Spring Harbor perspectives in biology · 2019
    Review
  15. Article
  16. Review
  17. Translation Termination and Ribosome Recycling in Eukaryotes.Cold Spring Harbor perspectives in biology · 2018
    Review
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

11 authors at 1 institution in 2 countries.

Mainul HoqueDepartment of Biochemistry & Molecular Biology, Rutgers New Jersey Medical School, Newark, NJ, USA.
Ji Yeon ParkDepartment of Biochemistry & Molecular Biology, Rutgers New Jersey Medical School, Newark, NJ, USA.
Yun-Juan ChangDepartment of Microbiology, Biochemistry & Molecular Genetics, Rutgers New Jersey Medical School, Newark, NJ, USA.
Augusto D LuchessiDepartment of Biochemistry & Molecular Biology, Rutgers New Jersey Medical School, Newark, NJ, USA.
Tavane D CambiaghiDepartment of Biochemistry & Molecular Biology, Rutgers New Jersey Medical School, Newark, NJ, USA.
Raghavendra ShamannaDepartment of Biochemistry & Molecular Biology, Rutgers New Jersey Medical School, Newark, NJ, USA.
Hartmut M Hanauske-AbelDepartment of Biochemistry & Molecular Biology, Rutgers New Jersey Medical School, Newark, NJ, USA.
Bart HollandDepartment of Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA.
Tsafi Pe'eryDepartment of Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA.
Bin TianDepartment of Biochemistry & Molecular Biology, Rutgers New Jersey Medical School, Newark, NJ, USA.
Michael B MathewsDepartment of Biochemistry & Molecular Biology, Rutgers New Jersey Medical School, Newark, NJ, USA.
Rutgers, The State University of New Jersey · US

Funding

Regulation of Alternative Cleavage and PolyadenylationR01GM084089 · NIGMS · WISTAR INSTITUTE · PI TIAN, BIN · 2008 to 2023
$6.7M
NIGMS NIH HHS R01 GM084089
6 · The paper itself

Abstract

Nonsense-mediated mRNA decay (NMD) couples protein synthesis to mRNA turnover. It eliminates defective transcripts and controls the abundance of certain normal mRNAs. Our study establishes a connection between NMD and the translation factor eIF5A (eukaryotic initiation factor 5A) in human cells. eIF5A modulates the synthesis of groups of proteins (the eIF5A regulon), and undergoes a distinctive two-step post-translational modification (hypusination) catalyzed by deoxyhypusine synthase and deoxyhypusine hydroxylase. We show that expression of NMD-susceptible constructs was increased by depletion of the major eIF5A isoform, eIF5A1. NMD was also attenuated when hypusination was inhibited by RNA interference with either of the two eIF5A modifying enzymes, or by treatment with the drugs ciclopirox or deferiprone which inhibit deoxyhypusine hydroxylase. Transcriptome analysis by RNA-Seq identified human genes whose expression is coordinately regulated by eIF5A1, its modifying enzymes, and the pivotal NMD factor, Upf1. Transcripts encoding components of the translation system were highly represented, including some encoding ribosomal proteins controlled by alternative splicing coupled to NMD (AS-NMD). Our findings extend and strengthen the association of eIF5A with NMD, previously inferred in yeast, and show that hypusination is important for this function of human eIF5A. In addition, they advance drug-mediated NMD suppression as a therapeutic opportunity for nonsense-associated diseases. We propose that regulation of mRNA stability contributes to eIF5A's role in selective gene expression.

Indexed as

drugeIF5Ahuman transcriptomehypusineNMDregulonRNA decaytherapytranslation factor

Identifiers

PMID29034140
PMCPMC5630042
OpenAlexW2749259413

What Socratic holds

Textmetadata
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 Socratic graph.