ArticlePLoS biology2006
High guanine and cytosine content increases mRNA levels in mammalian cells.
Article in PLoS biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 289 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
289 citing papers in PubMed, 2 syntheses or guidelines pooled it, 477 citations in OpenAlex.
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- Synonymous but Not Silent: The Codon Usage Code for Gene Expression and Protein Folding.Annual review of biochemistry · 2021Pooled it
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- Impact of GC content on de novo gene birth.Nature communications · 2026Article
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- Nuclear effects play an important role in determining codon usage-dependent human gene expression.Nature communications · 2025Article
- GC3 codons enhance protein production in diverse GC- and AT-rich plant species.bioRxiv : the preprint server for biology · 2025Article
- Deep generative optimization of mRNA codon sequences for enhanced mRNA translation and therapeutic efficacy.Nature communications · 2025Article
229 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mammalian genes are highly heterogeneous with respect to their nucleotide composition, but the functional consequences of this heterogeneity are not clear. In the previous studies, weak positive or negative correlations have been found between the silent-site guanine and cytosine (GC) content and expression of mammalian genes. However, previous studies disregarded differences in the genomic context of genes, which could potentially obscure any correlation between GC content and expression. In the present work, we directly compared the expression of GC-rich and GC-poor genes placed in the context of identical promoters and UTR sequences. We performed transient and stable transfections of mammalian cells with GC-rich and GC-poor versions of Hsp70, green fluorescent protein, and IL2 genes. The GC-rich genes were expressed several-fold to over a 100-fold more efficiently than their GC-poor counterparts. This effect was not due to different translation rates of GC-rich and GC-poor mRNA. On the contrary, the efficient expression of GC-rich genes resulted from their increased steady-state mRNA levels. mRNA degradation rates were not correlated with GC content, suggesting that efficient transcription or mRNA processing is responsible for the high expression of GC-rich genes. We conclude that silent-site GC content correlates with gene expression efficiency in mammalian cells.
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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.