High guanine and cytosine content increases mRNA levels in mammalian cells

• Published in: PLoS biology 2006-06, Vol.4 (6), p.e180-e180
• Main Authors: Kudla, Grzegorz, Lipinski, Leszek, Caffin, Fanny, Helwak, Aleksandra, Zylicz, Maciej
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions; Base Composition - physiology; Bias; Cell Biology; Chemical properties; Cytosine; Cytosine - analysis; GC Rich Sequence; Gene expression; Gene Expression Regulation; Genetic aspects; Genetics; Genetics/Genomics/Gene Therapy; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Guanine; Guanine - analysis; HeLa Cells; HSP70 Heat-Shock Proteins - genetics; HSP70 Heat-Shock Proteins - metabolism; Humans; In Vitro; Interleukin-2 - genetics; Interleukin-2 - metabolism; Mammals; Messenger RNA; Mutation; Physiological aspects; Promoter Regions, Genetic; Proteins; RNA Processing, Post-Transcriptional; RNA, Messenger - metabolism; Transcription, Genetic
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.0040180

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.