Homeostasis in the Central Dogma of molecular biology: the importance of mRNA instability

RNA Biol. 2019 Dec;16(12):1659-1666. doi: 10.1080/15476286.2019.1655352. Epub 2019 Sep 2.

Abstract

Cell survival requires the control of biomolecule concentration, i.e. biomolecules should approach homeostasis. With information-carrying macromolecules, the particular concentration variation ranges depend on each type: DNA is not buffered, but mRNA and protein concentrations are homeostatically controlled, which leads to the ribostasis and proteostasis concepts. In recent years, we have studied the particular features of mRNA ribostasis and proteostasis in the model organism S. cerevisiae. Here we extend this study by comparing published data from three other model organisms: E. coli, S. pombe and cultured human cells. We describe how mRNA ribostasis is less strict than proteostasis. A constant ratio appears between the average decay and dilution rates during cell growth for mRNA, but not for proteins. We postulate that this is due to a trade-off between the cost of synthesis and the response capacity. This compromise takes place at the transcription level, but is not possible at the translation level as the high stability of proteins, versus that of mRNAs, precludes it. We hypothesize that the middle-place role of mRNA in the Central Dogma of Molecular Biology and its chemical instability make it more suitable than proteins for the fast changes needed for gene regulation.

Keywords: Transcription; evolution; mrna stability; protein stability; proteostasis; ribostasis; translation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / genetics*
  • DNA / metabolism
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Evolution, Molecular
  • Gene Expression Regulation
  • HeLa Cells
  • Homeostasis / genetics*
  • Humans
  • Proteins / genetics*
  • Proteins / metabolism
  • Proteostasis / genetics
  • RNA Stability*
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / metabolism
  • Transcription, Genetic*

Substances

  • Proteins
  • RNA, Messenger
  • DNA

Grants and funding

This work has been supported by grants from the Spanish Ministry of Economy and Competitiveness, and European Union funds (FEDER) [BFU2016-77728-C3-1-P to S. C.], from Regional Andalusian Government [P12-BIO1938MO to S.C.] [BFU2016-77728-C3-3-P and BFU2015-71978-REDT to J.E.P-O] and from the Regional Valencian Government [PROMETEO II 2015/006 to J.E.P-O].