The kinetics of mammalian gene expression

Abstract

When rates of transcription from specific genes change, delays of variable length intervene before the corresponding mRNAs and proteins attain new levels. For most mammalian genes, the time required to complete transcription, processing, and transport of mRNA is much shorter than the period needed to achieve a new, steady-state level of protein. Studies of inducible genes have shown that the period required to attain new levels of individual mRNAs and proteins is related to their unique half-lives. The basis for this is a physical principle that predicts rates of accumulation of particles in compartmental systems. The minimum period required to achieve a new level is directly proportional to product half-lives because rates of decay control the ratio between the rate of synthesis and the concentration of gene products at steady state. This kinetic model suggests that sensitivity of gene products to degradation by ribonucleases and proteinases is an important determinant of the time scale of gene expression.

Genomics and gene transcription kinetics in yeast

“…If a given mRNA is in a steady state at a concentration mI, and it is compelled to change its concentration to reach a new steady-state level, mF, by changing its transcription rate (TR) from TRI to TRF, then the mRNA concentration varies exponentially with time (t) according to: It can be seen from Equation 3 that the time required for readjustment depends only on k (i.e. on the mRNA half-life) [7,9] As mentioned, mRNA concentration depends on both the synthesis rate and the degradation rate. Therefore, cells can use different strategies to increase or decrease mRNA concentrations, by modifying TR and/or k. In this section, we examine the consequences of these different strategies with regard to transition speed and synthetic cost.…”

“…The synthesis of both mRNA and protein follows zero-order kinetics (see Glossary), whereas their decay follows first-order kinetics [7,9]. Thus, the concentration of either of these macromolecules at a steady state (Css), when rates of synthesis and degradation are equal, can be expressed as a ratio of the rate constant for synthesis (ks) to the rate constant for decay (k): …”

“…RNA polymerase II has been calculated to travel at ~18-42 nucleotides per second on chromatin templates [1][2][3][4][5]. This speed might not be constant across all genes and conditions, but if we take it to be a representative average value, then the time required to 'read' a gene is not negligible: 25-50 seconds for 1 kb (the average length of a yeast gene [6]); 2-3 minutes for a typical mammalian gene [7]; and up to 16 hours for certain long intron-containing human genes [3]. Pausing and termination further delay the release of mRNA molecules from the genes (as discussed in Ref.…”

“…If a given mRNA is in a steady state at a concentration mI, and it is compelled to change its concentration to reach a new steady-state level, mF, by changing its transcription rate (TR) from TRI to TRF, then the mRNA concentration varies exponentially with time (t) according to: It can be seen from Equation 3 that the time required for readjustment depends only on k (i.e. on the mRNA half-life) [7,9]. However, mF depends on TRF because the steady-state relationship (Equation 1) applies to the new steady state; that is:…”

Identification and cDNA Cloning of a Novel RNA-binding Protein That Interacts with the Cyclic Nucleotide-responsive Sequence in the Type-1 Plasminogen Activator Inhibitor mRNA

“…Regulation of mRNA stability is an important component of the regulation of gene expression and is known to have a significant role in normal physiology and development (1)(2)(3)(4)(5). Our understanding of the regulation of message degradation has been enhanced by the identification of consensus cis-acting sequences that are involved in determining message stability and of some proteins that interact with them (4,6).…”