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Translational repression contributes greater noise to gene expression than transcriptional repression.

ABSTRACT: Stochastic effects in gene expression may result in different physiological states of individual cells, with consequences for pathogen survival and artificial gene network design. We studied the contributions of a regulatory factor to gene expression noise in four basic mechanisms of negative gene expression control: 1), transcriptional regulation by a protein repressor, 2), translational repression by a protein; 3), transcriptional repression by RNA; and 4), RNA interference with the translation. We investigated a general model of a two-gene network, using the chemical master equation and a moment generating function approach. We compared the expression noise of genes with the same effective transcription and translation initiation rates resulting from the action of different repressors, whereas previous studies compared the noise of genes with the same mean expression level but different initiation rates. Our results show that translational repression results in a higher noise than repression on the promoter level, and that this relationship does not depend on quantitative parameter values. We also show that regulation of protein degradation contributes more noise than regulated degradation of mRNA. These are unexpected results, because previous investigations suggested that translational regulation is more accurate. The relative magnitude of the noise introduced by protein and RNA repressors depends on the protein and mRNA degradation rates, and we derived expressions for the threshold below which the noise introduced by a protein repressor is higher than the noise introduced by an RNA repressor.

SUBMITTER: Komorowski M

PROVIDER: S-EPMC2716471 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

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Translational repression contributes greater noise to gene expression than transcriptional repression.

Komorowski Michał M Miekisz Jacek J Kierzek Andrzej M AM

Biophysical journal 20090101 2

Stochastic effects in gene expression may result in different physiological states of individual cells, with consequences for pathogen survival and artificial gene network design. We studied the contributions of a regulatory factor to gene expression noise in four basic mechanisms of negative gene expression control: 1), transcriptional regulation by a protein repressor, 2), translational repression by a protein; 3), transcriptional repression by RNA; and 4), RNA interference with the translatio ...[more]

PMID: 19167290

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Project description:Toxoplasma gondii is a widespread protozoan parasite that has a significant impact on human and veterinary health. The parasite undergoes a complex life cycle involving multiple hosts and developmental stages. How Toxoplasma transitions between life cycle stages is poorly understood yet central to controlling transmission. Of particular neglect are the factors that contribute to its sexual development, which takes place exclusively in feline intestines. While epigenetic repressors have been shown to play an important role in silencing the spurious gene expression of sexually committed parasites, the specific factors that recruit this generalized machinery to the appropriate genes remain largely unexplored. Here, we establish that a member of the AP2 transcription factor family, AP2XII-2, is targeted to genomic loci associated with sexually committed parasites along with epigenetic regulators of transcriptional silencing, HDAC3 and MORC. Despite its widespread association with gene promoters, AP2XII-2 is required for the silencing of relatively few genes. Using the CUT&Tag (cleavage under targets and tagmentation) methodology, we identify two major genes associated with sexual development downstream of AP2XII-2 control, AP2X-10 and the amino acid hydroxylase AAH1. Our findings show that AP2XII-2 is a key contributor to the gene regulatory pathways modulating Toxoplasma sexual development. IMPORTANCE Toxoplasma gondii is a parasite that undergoes its sexual stage exclusively in feline intestines, making cats a major source of transmission. A better understanding of the proteins controlling the parasite's life cycle stage transitions is needed for the development of new therapies aimed at treating toxoplasmosis and the transmission of the infection. Genes that regulate the sexual stages need to be turned on and off at the appropriate times, activities that are mediated by specific transcription factors that recruit general machinery to silence or activate gene expression. In this study, we identify a transcription factor called AP2XII-2 as being important for the repression of a subset of sexual stage genes, including a sexual stage-specific AP2 factor (AP2X-10) and a protein (AAH1) required to construct the infectious oocysts expelled from infected cats.

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Translational repression contributes greater noise to gene expression than transcriptional repression.

Publications

Translational repression contributes greater noise to gene expression than transcriptional repression.

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