ArticleGenome biology2021
A trans locus causes a ribosomopathy in hypertrophic hearts that affects mRNA translation in a protein length-dependent fashion.
Article in Genome biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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.
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.
Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- The emerging roles of small nucleolar RNAs, piwi-interacting RNAs, tRNA-derived small RNAs, and circular RNAs in the regulation of cardiac hypertrophy, ischemic heart disease, and heart failure.Genes & diseases · 2026Review
- Predicting the translation efficiency of messenger RNA in mammalian cells.Nature biotechnology · 2026Article
- Translational Control in Cardiac Pathophysiology and Therapeutic Development: When mRNA Meets the Heart.International journal of molecular sciences · 2025Review
- Unlocking the life code: a review of SnoRNA functional diversity and disease relevance.Cell communication and signaling : CCS · 2025Review
- The SHR/Akr Y chromosome reveals repeated turnover of the rat pseudoautosomal region.bioRxiv : the preprint server for biology · 2025Article
- Evolution of translational control and the emergence of genes and open reading frames in human and non-human primate hearts.Nature cardiovascular research · 2024Article
- A revamped rat reference genome improves the discovery of genetic diversity in laboratory rats.Cell genomics · 2024Article
- A revamped rat reference genome improves the discovery of genetic diversity in laboratory rats.bioRxiv : the preprint server for biology · 2023Article
- Evolutionary origins and interactomes of human, young microproteins and small peptides translated from short open reading frames.Molecular cell · 2023Article
- Cap analysis of gene expression reveals alternative promoter usage in a rat model of hypertension.Life science alliance · 2022Article
- A trans locus causes a ribosomopathy in hypertrophic hearts that affects mRNA translation in a protein length-dependent fashion.Genome biology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 7 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLittle is known about the impact of trans-acting genetic variation on the rates with which proteins are synthesized by ribosomes. Here, we investigate the influence of such distant genetic loci on the efficiency of mRNA translation and define their contribution to the development of complex disease phenotypes within a panel of rat recombinant inbred lines.
resultsWe identify several tissue-specific master regulatory hotspots that each control the translation rates of multiple proteins. One of these loci is restricted to hypertrophic hearts, where it drives a translatome-wide and protein length-dependent change in translational efficiency, altering the stoichiometric translation rates of sarcomere proteins. Mechanistic dissection of this locus across multiple congenic lines points to a translation machinery defect, characterized by marked differences in polysome profiles and misregulation of the small nucleolar RNA SNORA48. Strikingly, from yeast to humans, we observe reproducible protein length-dependent shifts in translational efficiency as a conserved hallmark of translation machinery mutants, including those that cause ribosomopathies. Depending on the factor mutated, a pre-existing negative correlation between protein length and translation rates could either be enhanced or reduced, which we propose to result from mRNA-specific imbalances in canonical translation initiation and reinitiation rates.
conclusionsWe show that distant genetic control of mRNA translation is abundant in mammalian tissues, exemplified by a single genomic locus that triggers a translation-driven molecular mechanism. Our work illustrates the complexity through which genetic variation can drive phenotypic variability between individuals and thereby contribute to complex disease.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.