Evidence map›Paper›PMID 31109297›Full record

ArticleBMC genomics2019

Translation of upstream open reading frames in a model of neuronal differentiation.

Caitlin M Rodriguez, Sang Y Chun, Ryan E Mills, Peter K Todd

Open access · goldAbstract read
In one paragraph

Article in BMC genomics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.2field-weighted citation impact, top 11% 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

30 citing papers in PubMed, 41 citations in OpenAlex.

  1. Article
  2. An upstream open reading frame represses translation of the neuronal potassium channel KCNQ2.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  14. Evaluation of the SH-SY5Y cell line as anFrontiers in molecular neuroscience · 2023
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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

4 authors at 1 institution in 1 country.

Caitlin M RodriguezDepartment of Neurology, University of Michigan, Ann Arbor, MI, USA.
Sang Y ChunDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, 48109, USA.
Ryan E MillsDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, 48109, USA. remills@umich.edu.
Peter K ToddDepartment of Neurology, University of Michigan, Ann Arbor, MI, USA. petertod@med.umich.edu.ORCID http://orcid.org/0000-0003-4781-6376
University of Michigan · US

Funding

Hexanucleotide repeat translation in ALS and Frontotemporal DementiaR01NS099280 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Peter K Todd · 2016 to 2026
$4.9M
CGG repeat associated translation in Fragile X-associated Tremor/Ataxia Syndrome-Diversity SupplementR01NS086810 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI TODD, PETER K · 2014 to 2024
$4.1M
Proteogenomics of Cancer Training ProgramT32CA140044 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI RAO, ARVIND, SARTOR, MAUREEN AGNES · 2010 to 2024
$3.9M
Early Stage Training in the NeurosciencesT32NS076401 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Carol Fuzeti Elias, LESLIE S. SATIN · 2011 to 2026
$3.1M
Discovery and analysis of structural variation in whole genome sequencesR01HG007068 · NHGRI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MILLS, RYAN E · 2013 to 2016
$1.5M
Upstream open reading frames in neuronal function: a singular and genome-wide approachF31NS090883 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI RODRIGUEZ, CAITLIN MARIE · 2014 to 2017
$102k
RNA Dominant Mechanisms in ALSI21BX001841 · VA · VETERANS HEALTH ADMINISTRATION · PI TODD, PETER K · 2014 to 2015
–
RAN translation in C9orf72 repeat associated ALS and FTDI01BX003231 · VA · VETERANS HEALTH ADMINISTRATION · PI TODD, PETER K · 2017 to 2018
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BLRD VA I01 BX003231BLRD VA I21 BX001841NCI NIH HHS T32 CA140044NHGRI NIH HHS R01 HG007068NHGRI NIH HHS R01HG007068NIH HHS F31NS090883NIH HHS T32CA140044NINDS NIH HHS F31 NS090883NINDS NIH HHS R01 NS086810NINDS NIH HHS R01NS086810NINDS NIH HHS R01 NS099280
6 · The paper itself

Abstract

backgroundUpstream open reading frames (uORFs) initiate translation within mRNA 5' leaders, and have the potential to alter main coding sequence (CDS) translation on transcripts in which they reside. Ribosome profiling (RP) studies suggest that translating ribosomes are pervasive within 5' leaders across model systems. However, the significance of this observation remains unclear. To explore a role for uORF usage in a model of neuronal differentiation, we performed RP on undifferentiated and differentiated human neuroblastoma cells.

resultsUsing a spectral coherence algorithm (SPECtre), we identify 4954 consistently translated uORFs across 31% of all neuroblastoma transcripts. These uORFs predominantly utilize non-AUG initiation codons and exhibit translational efficiencies (TE) comparable to annotated coding regions. On a population basis, the global impact of both AUG and non-AUG initiated uORFs on basal CDS translation were small, even when analysis is limited to conserved and consistently translated uORFs. However, uORFs did alter the translation of a subset of genes, including the Diamond-Blackfan Anemia associated ribosomal gene RPS24. With retinoic acid induced differentiation, we observed an overall positive correlation in translational shifts between uORF/CDS pairs. However, CDSs downstream of uORFs show smaller shifts in TE with differentiation relative to CDSs without a predicted uORF, suggesting that uORF translation buffers cell state dependent fluctuations in CDS translation.

conclusionThis work provides insights into the dynamic relationships and potential regulatory functions of uORF/CDS pairs in a model of neuronal differentiation.

Indexed as

Open Reading FramesProtein BiosynthesisAlgorithmsCell DifferentiationCell Line, TumorGene Expression RegulationHumansModels, BiologicalNeuronsRibosomes5′ untranslated regionNear-cognate start codonNeuronal differentiationRibosome profilingTranslationUpstream open reading frame

Identifiers

PMID31109297
PMCPMC6528255
OpenAlexW2949452190

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.