TY - JOUR
T1 - Teasing Apart Translational and Transcriptional Components of Stochastic Variations in Eukaryotic Gene Expression
AU - Salari, Raheleh
AU - Wojtowicz, Damian
AU - Zheng, Jie
AU - Levens, David
AU - Pilpel, Yitzhak
AU - Przytycka, Teresa M.
N1 - Intramural Program of National Institutes of Health NLM; NCI; CCR; Polish Ministry of Science and Higher Education [NN301065236]; European Research Council; Ben May Foundation; Nanyang Technological University, Singapore [M4080108.020]The research was supported in part by the Intramural Program of National Institutes of Health NLM (RS, JZ, DW, TMP) and NCI, CCR (DL), as well as in part by a grant from the Polish Ministry of Science and Higher Education (NN301065236) to DW. YP is supported by an "Ideas" grant of the European Research Council and the Ben May Foundation. JZ was also supported in part by start-up grant (M4080108.020) at Nanyang Technological University, Singapore. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
PY - 2012/8
Y1 - 2012/8
N2 - The intrinsic stochasticity of gene expression leads to cell-to-cell variations, noise, in protein abundance. Several processes, including transcription, translation, and degradation of mRNA and proteins, can contribute to these variations. Recent single cell analyses of gene expression in yeast have uncovered a general trend where expression noise scales with protein abundance. This trend is consistent with a stochastic model of gene expression where mRNA copy number follows the random birth and death process. However, some deviations from this basic trend have also been observed, prompting questions about the contribution of gene-specific features to such deviations. For example, recent studies have pointed to the TATA box as a sequence feature that can influence expression noise by facilitating expression bursts. Transcription-originated noise can be potentially further amplified in translation. Therefore, we asked the question of to what extent sequence features known or postulated to accompany translation efficiency can also be associated with increase in noise strength and, on average, how such increase compares to the amplification associated with the TATA box. Untangling different components of expression noise is highly nontrivial, as they may be gene or gene-module specific. In particular, focusing on codon usage as one of the sequence features associated with efficient translation, we found that ribosomal genes display a different relationship between expression noise and codon usage as compared to other genes. Within nonribosomal genes we found that sequence high codon usage is correlated with increased noise relative to the average noise of proteins with the same abundance. Interestingly, by projecting the data on a theoretical model of gene expression, we found that the amplification of noise strength associated with codon usage is comparable to that of the TATA box, suggesting that the effect of translation on noise in eukaryotic gene expression might be more prominent than previously appreciated.
AB - The intrinsic stochasticity of gene expression leads to cell-to-cell variations, noise, in protein abundance. Several processes, including transcription, translation, and degradation of mRNA and proteins, can contribute to these variations. Recent single cell analyses of gene expression in yeast have uncovered a general trend where expression noise scales with protein abundance. This trend is consistent with a stochastic model of gene expression where mRNA copy number follows the random birth and death process. However, some deviations from this basic trend have also been observed, prompting questions about the contribution of gene-specific features to such deviations. For example, recent studies have pointed to the TATA box as a sequence feature that can influence expression noise by facilitating expression bursts. Transcription-originated noise can be potentially further amplified in translation. Therefore, we asked the question of to what extent sequence features known or postulated to accompany translation efficiency can also be associated with increase in noise strength and, on average, how such increase compares to the amplification associated with the TATA box. Untangling different components of expression noise is highly nontrivial, as they may be gene or gene-module specific. In particular, focusing on codon usage as one of the sequence features associated with efficient translation, we found that ribosomal genes display a different relationship between expression noise and codon usage as compared to other genes. Within nonribosomal genes we found that sequence high codon usage is correlated with increased noise relative to the average noise of proteins with the same abundance. Interestingly, by projecting the data on a theoretical model of gene expression, we found that the amplification of noise strength associated with codon usage is comparable to that of the TATA box, suggesting that the effect of translation on noise in eukaryotic gene expression might be more prominent than previously appreciated.
UR - http://www.scopus.com/inward/record.url?scp=84866082847&partnerID=8YFLogxK
U2 - https://doi.org/10.1371/journal.pcbi.1002644
DO - https://doi.org/10.1371/journal.pcbi.1002644
M3 - مقالة
SN - 1553-734X
VL - 8
JO - PLoS Computational Biology
JF - PLoS Computational Biology
IS - 8
M1 - e1002644
ER -