Evidence map›Paper›PMID 28334758›Full record

ArticleNucleic acids research2017

N1-methyl-pseudouridine in mRNA enhances translation through eIF2α-dependent and independent mechanisms by increasing ribosome density.

Yuri V Svitkin, Yi Min Cheng, Tirtha Chakraborty, Vladimir Presnyak, Matthias John, Nahum Sonenberg

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 181 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
181citing papers in PubMed, 1 pooled it
5.6field-weighted citation impact, top 3% 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

181 citing papers in PubMed, 1 synthesis or guideline pooled it, 262 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Review
  6. Towards mRNA therapeutics 2.0.Nature reviews. Drug discovery · 2026
    Review
  7. Recoding by NNature communications · 2026
    Article
  8. Review
  9. NNature · 2026
    Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. RiboScreenBiomedicines · 2026
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Review

121 more citing papers are in PubMed but not listed here.

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

6 authors at 2 institutions in 2 countries.

Yuri V SvitkinDepartment of Biochemistry, McGill University, Montréal, Québec H3A 1A3, Canada.
Yi Min ChengModerna Therapeutics, Cambridge, MA 02139, USA.
Tirtha ChakrabortyModerna Therapeutics, Cambridge, MA 02139, USA.
Vladimir PresnyakModerna Therapeutics, Cambridge, MA 02139, USA.
Matthias JohnModerna Therapeutics, Cambridge, MA 02139, USA.
Nahum SonenbergDepartment of Biochemistry, McGill University, Montréal, Québec H3A 1A3, Canada.
Moderna Therapeutics (United States) · USMcGill University · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Certain chemical modifications confer increased stability and low immunogenicity to in vitro transcribed mRNAs, thereby facilitating expression of therapeutically important proteins. Here, we demonstrate that N1-methyl-pseudouridine (N1mΨ) outperforms several other nucleoside modifications and their combinations in terms of translation capacity. Through extensive analysis of various modified transcripts in cell-free translation systems, we deconvolute the different components of the effect on protein expression independent of mRNA stability mechanisms. We show that in addition to turning off the immune/eIF2α phosphorylation-dependent inhibition of translation, the incorporated N1mΨ nucleotides dramatically alter the dynamics of the translation process by increasing ribosome pausing and density on the mRNA. Our results indicate that the increased ribosome loading of modified mRNAs renders them more permissive for initiation by favoring either ribosome recycling on the same mRNA or de novo ribosome recruitment.

Indexed as

Protein BiosynthesisAnimalsCell-Free SystemCell LineeIF-2 KinaseEnzyme ActivationEukaryotic Initiation Factor-2FibroblastsHEK293 CellsHeLa CellsHumansMicePhosphorylationPolyribosomesProtein Processing, Post-TranslationalPseudouridine1-methylpseudouridineeIF-2 KinaseEukaryotic Initiation Factor-2PseudouridineRNARNA, MessengerRNA, recombinant

Identifiers

PMID28334758
PMCPMC5449617
OpenAlexW2589945527

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.