Evidence map›Paper›PMID 38971149›Full record

ArticleCell systems2024

SEMPER: Stoichiometric expression of mRNA polycistrons by eukaryotic ribosomes for compact, ratio-tunable multi-gene expression.

Mengtong Duan, Ishaan Dev, Andrew Lu, Goar Ayrapetyan, Mei Yi You, Mikhail G Shapiro

Abstract read
In one paragraph

Article in Cell systems, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
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

10 citing papers in PubMed.

  1. Article
  2. Split genetically encoded calcium indicators for interorganellar junctions.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  3. Article
  4. Leaky ribosomal scanning enables tunable translation of bicistronic ORFs in green algae.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  5. Article
  6. Article
  7. Perspectives on Synthetic Protein Circuits in Mammalian Cells.Current opinion in biomedical engineering · 2024
    Article
  8. Article
  9. Article
  10. 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

6 authors.

Mengtong DuanDivision of Biology and Biological Engineering, Caltech, Pasadena, CA 91125, USA.
Ishaan DevDivision of Chemistry and Chemical Engineering, Caltech, Pasadena, CA 91125, USA.
Andrew LuDivision of Biology and Biological Engineering, Caltech, Pasadena, CA 91125, USA; UCLA-Caltech Medical Scientist Training Program, UCLA, Los Angeles, CA 90095, USA.
Goar AyrapetyanDivision of Chemistry and Chemical Engineering, Caltech, Pasadena, CA 91125, USA.
Mei Yi YouDivision of Biology and Biological Engineering, Caltech, Pasadena, CA 91125, USA.
Mikhail G ShapiroDivision of Chemistry and Chemical Engineering, Caltech, Pasadena, CA 91125, USA; Andrew and Peggy Cherng Department of Medical Engineering, Caltech, Pasadena, CA 91125, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: mikhail@caltech.edu.

Funding

UCLA-Caltech Medical Scientist Training ProgramT32GM008042 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AJIJOLA, OLUJIMI A, DAWSON, DAVID WAYNE · 1985 to 2023
$29.9M
Biogenic Gas Nanostructures As Molecular Imaging Reporters For UltrasoundR01EB018975 · NIBIB · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI Mikhail Shapiro · 2014 to 2026
$5.9M
NIBIB NIH HHS R01 EB018975NIGMS NIH HHS T32 GM008042
6 · The paper itself

Abstract

Here, we present a method for expressing multiple open reading frames (ORFs) from single transcripts using the leaky scanning model of translation initiation. In this approach termed "stoichiometric expression of mRNA polycistrons by eukaryotic ribosomes" (SEMPER), adjacent ORFs are translated from a single mRNA at tunable ratios determined by their order in the sequence and the strength of their translation initiation sites. We validate this approach by expressing up to three fluorescent proteins from one plasmid in two different cell lines. We then use it to encode a stoichiometrically tuned polycistronic construct encoding gas vesicle acoustic reporter genes that enables efficient formation of the multi-protein complex while minimizing cellular toxicity. We also demonstrate that SEMPER enables polycistronic expression of recombinant monoclonal antibodies from plasmid DNA and of two fluorescent proteins from single mRNAs made through in vitro transcription. Finally, we provide a probabilistic model to elucidate the mechanisms underlying SEMPER. A record of this paper's transparent peer review process is included in the supplemental information.

Indexed as

Open Reading FramesRibosomesRNA, MessengerAnimalsGene ExpressionGenes, ReporterHumansPlasmidsProtein BiosynthesisRNA, Messengeracoustic reportercircuiteukaryotesgas vesiclegene expressionin vitro transcriptionmammalian cellmonoclonal antibodiesMonte CarlomRNApolycistronicratiosynthetic biologytoxicitytunable

Identifiers

PMID38971149
PMCPMC11298409

What OpenQuestion holds

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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.