Control of Ribosomal RNA Transcription by Nutrients

Abstract

The ribosome is a unique machine for protein synthesis in organisms. The construction of ribosomes is exceedingly complex and consumes the majority of the cell materials and energy. The materials for ribosome production are supplied by nutrients. Therefore, the production of ribosomes is restricted by environmental nutrients, and cells need mechanisms to control ribosome production in order to reconcile demands for cell activities with available resources. Transcription of ribosomal RNA is an essential step in ribosome biogenesis. It strongly affects the total amount of ribosome production, and thus rapidly growing cells have an elevated level of ribosomal RNA transcription. Ribosomal RNA transcription is controlled by many mechanisms, including the efficiency of preinitiation complex formation for RNA polymerase I (Pol I) and epigenetic marks in ribosomal RNA genes. These are affected by cell cycle progression, signal transduction pathways, cell-damaging stresses, nutrients such as glucose, and the metabolites. Recent studies also suggest that the epigenetic marks, acetylation and methylation, may be not only controlled by nutrients but also function as reservoirs for biological resources in chromatin. Further studies would provide information about the mechanisms cells use to adjust production of cellular components to available resources and clues for developing novel anti-cancer treatments.

Environmental Exposures around Conception: Developmental Pathways Leading to Lifetime Disease Risk

“…The ribosome is the cellular protein translation machine that controls growth across the whole organism and throughout life. Whilst there are several hundreds of rDNA gene copies available per cell, many are inactive physiologically through epigenetic mechanisms, and thus, the rate of transcription can be modulated by nutrient availability and other factors such as ageing [90][91][92]. rDNA silencing includes epigenetic regulation through hypermethylation of the rDNA promotor restricting Pol 1 binding and transcription, working alongside ribosome-associated proteins that coordinate Pol 1 activity and sense cellular environment [91,93].…”

“…Lastly, we need to consider how environmental nutrient availability is perceived to regulate RRN3 expression and ribosome biogenesis. RRN3 expression is regulated by environmental factors, reduced by caloric and other nutrient restriction and sensitive to AA availability and mTORC1 signalling [91,92,102]. Indeed, PTEN, the negative regulator of mTORC1, has been proposed as a thrifty gene to drive metabolic storage when nutrients are plentiful [103].…”

Aging and Caloric Restriction Modulate the DNA Methylation Profile of the Ribosomal RNA Locus in Human and Rat Liver

“…rRNA is the most abundant transcript of the cell and, as such, its transcription is highly energy consuming. In line with what is discussed above, rDNA transcription is modulated according to different environmental factors, like the regulators of cell cycle, growth factors, stressors, and nutrients, to guarantee energy homeostasis [26]. In particular, several studies reported that amino acid/glucose starvation and CR reduce rDNA transcription in yeast and mammal cells [26][27][28][29][30].…”

Metformin activates KDM2A to reduce rRNA transcription and cell proliferation by dual regulation of AMPK activity and intracellular succinate level

“…The ribosome is a unique machine to synthesize proteins in organisms 13,14 , and the control of ribosome biogenesis is a critical factor in the regulation of cellular activities 15–18 . Because the level of rRNA transcription is a major factor determining the production of ribosomes, the regulation of rRNA transcription affects multiple cellular activities, including cell proliferation 13,14,16,18–23 . Recently, increasing numbers of studies have shown that epigenetic regulators control rRNA transcription 13,14,23–27 .…”

“…Because the level of rRNA transcription is a major factor determining the production of ribosomes, the regulation of rRNA transcription affects multiple cellular activities, including cell proliferation 13,14,16,18–23 . Recently, increasing numbers of studies have shown that epigenetic regulators control rRNA transcription 13,14,23–27 . We previously showed that a JmjC histone demethylase, lysine-demethylase 2 A (KDM2A), decreases the dimethylated lysine 36 of histone H3 (H3K36me2) in the ribosome RNA gene (rDNA) promoter and represses rRNA transcription under starvation in breast cancer cells 28,29 .…”