Evidence map›Paper›PMID 31855834›Full record

ArticleMolecular therapy. Nucleic acids2020

In Vivo RNAi-Mediated eIF3m Knockdown Affects Ribosome Biogenesis and Transcription but Has Limited Impact on mRNA-Specific Translation.

Elena M Smekalova, Maxim V Gerashchenko, Patrick B F O'Connor, Charles A Whittaker, Kevin J Kauffman, Anna S Fefilova, Timofei S Zatsepin, Roman L Bogorad, Pavel V Baranov, Robert Langer and 3 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy. Nucleic acids, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

9 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. 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

13 authors at 7 institutions in 3 countries.

Elena M SmekalovaDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Maxim V GerashchenkoDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Patrick B F O'ConnorSchool of Biochemistry and Cell Biology, University College Cork, Cork T12 YN60, Ireland.
Charles A WhittakerDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Kevin J KauffmanDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Anna S FefilovaSkolkovo Institute of Science and Technology, Skolkovo, Moscow, 121205, Russia.
Timofei S ZatsepinSkolkovo Institute of Science and Technology, Skolkovo, Moscow, 121205, Russia; Department of Chemistry and Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119234, Russia.
Roman L BogoradDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Pavel V BaranovSchool of Biochemistry and Cell Biology, University College Cork, Cork T12 YN60, Ireland; Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, RAS, Moscow 117997, Russia.
Robert LangerDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA; Institute of Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
Vadim N GladyshevDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Daniel G AndersonDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA; Institute of Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: dgander@mit.edu.
Victor KotelianskySkolkovo Institute of Science and Technology, Skolkovo, Moscow, 121205, Russia. Electronic address: kotelianskiv@gmail.com.
Massachusetts Institute of Technology · USHarvard–MIT Division of Health Sciences and Technology · USHarvard University · USSkolkovo Institute of Science and Technology · RUInstitute of Bioorganic Chemistry · RULomonosov Moscow State University · RUUniversity College Cork · IE

Funding

Functions of thioredoxin reductases and their targetsR37GM065204 · NIGMS · BRIGHAM AND WOMEN'S HOSPITAL · PI GLADYSHEV, VADIM N. · 2011 to 2020
$4.0M
Systems level understanding of selenoprotein biosynthesisR01DK117149 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI GLADYSHEV, VADIM N. · 2018 to 2022
$2.4M
Functions of Mammalian Thioredoxin ReductasesR01GM065204 · NIGMS · UNIVERSITY OF NEBRASKA LINCOLN · PI GLADYSHEV, VADIM N. · 2002 to 2009
$2.2M
NIDDK NIH HHS R01 DK117149NIGMS NIH HHS R01 GM065204NIGMS NIH HHS R37 GM065204
6 · The paper itself

Abstract

Translation is an essential biological process, and dysregulation is associated with a range of diseases including ribosomopathies, diabetes, and cancer. Here, we examine translation dysregulation in vivo using RNAi to knock down the m-subunit of the translation initiation factor eIF3 in the mouse liver. Transcriptome sequencing, ribosome profiling, whole proteome, and phosphoproteome analyses show that eIF3m deficiency leads to the transcriptional response and changes in cellular translation that yield few detectable differences in the translation of particular mRNAs. The transcriptional response fell into two main categories: ribosome biogenesis (increased transcription of ribosomal proteins) and cell metabolism (alterations in lipid, amino acid, nucleic acid, and drug metabolism). Analysis of ribosome biogenesis reveals inhibition of rRNA processing, highlighting decoupling of rRNA synthesis and ribosomal protein gene transcription in response to eIF3m knockdown. Interestingly, a similar reduction in eIF3m protein levels is associated with induction of the mTOR pathway in vitro but not in vivo. Overall, this work highlights the utility of a RNAi-based in vivo approach for studying the regulation of mammalian translation in vivo.

Indexed as

eIF3eIF3min vivolivermTORribosomal genesribosome profilingrRNAsiRNAtranslation

Identifiers

PMID31855834
PMCPMC6926209
OpenAlexW2990079676

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.