Giving your mRNA a boost by increasing GC content

Abstract from PLoS (the abstract says it all):

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.

Very Interesting. High GC content at codon position #3, led to higher protein content, higher mRNA content, but no change in mRNA degradation. Unfortunately the authors did not test whether the mRNAs were transcribed more efficiently. Other possibilities is that mRNA 3' processing is inefficient or mRNA export is compromised (with the unexported mRNA being degraded immediately).

It's something to think about when designing your own genes. This finding also has implications for biologists who track mutations at synonymous sites ... although these mutations may be "silent" in how they change the coding of a protein, they may not be so silent (different use of the term) with regards to how they affect protein expression. This may also be a way of generating variability with regards to protein expression between different alleles. On the other hand, the effects of one point mutation may be very small. Is it too small to be selected on? We'll see.

Kudla G, Lipinski L, Caffin F, Helwak A, Zylicz M (2006) High Guanine and Cytosine Content Increases mRNA Levels in Mammalian Cells. PLoS Biol 4(6): e180

Cross posted at Daily Transcript.


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