Coupling of Ribosome Synthesis and Translational Capacity with Cell Growth

Dai, Xiongfeng; Zhu, Manlu

doi:10.1016/j.tibs.2020.04.010

Cited by 70 publications

(84 citation statements)

References 98 publications

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“…There the authors demonstrated that ribosomal proteome fractions in budding yeast are proportional to cellular growth rates, as previously observed for Bacteria [19,20]. Underlying this proportionality is the coupling between cell growth and ribosome biogenesis [21], i.e. that cell doubling requires a commensurate doubling of ribosomes.…”

Section: Introductionsupporting

confidence: 53%

“…Finally, it would be interesting to see whether similar growth-laws and invariants hold for higher, more evolved Eukarya, as these share many features of ribosome biogenesis with lower Eukarya and the eukaryotic core proteome appears to be quite stable across species [49]. Particularly interesting in this regard are cancer cells which exhibit rapid cell proliferation like Bacteria and yeast [14,21]. Hyperactivated ribosome production is a known signature of rapidly proliferating cancer cells [21,50].…”

Section: Discussionmentioning

confidence: 99%

“…Particularly interesting in this regard are cancer cells which exhibit rapid cell proliferation like Bacteria and yeast [14,21]. Hyperactivated ribosome production is a known signature of rapidly proliferating cancer cells [21,50]. During tumorigenesis, excessive rRNA transcription leads to enlarged nucleoli, which are the primary sites of ribosome biogenesis in the eukaryotic cell [51].…”

Section: Discussionmentioning

confidence: 99%

“…Verification will require simultaneous measurements of the growth rate and all parameters in Eqs. (21), (23), and (24), in various growth conditions. However, even for a well-studied model organism like S. cerevisiae, such a dataset is currently unavailable.…”

Section: Graphical Representation Of Boundsmentioning

confidence: 99%

“…Bounds on cellular growth rate from the production of r-protein (orange), 35S-derived rRNA (green), and 5S rRNA (blue). (a) We plot the three bounds [Eqs (21),(23),(24)(20)…”

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confidence: 99%

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Growth-laws and invariants from ribosome biogenesis in lower Eukarya

Kostinski

Reuveni

2020

Preprint

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Eukarya and Bacteria are the most evolutionarily distant domains of life, which is reflected by differences in their cellular structure and physiology. For example, Eukarya feature membrane-bound organelles such as nuclei and mitochondria, whereas Bacteria have none. The greater complexity of Eukarya renders them difficult to study from both an experimental and theoretical perspective. However, encouraged by a recent experimental result showing that budding yeast (a unicellular eukaryote) obeys the same proportionality between ribosomal proteome fractions and cellular growth rates as Bacteria, we derive a set of relations describing eukaryotic growth from first principles of ribosome biogenesis. We recover the observed ribosomal protein proportionality, and then continue to obtain two growth-laws for the number of RNA polymerases synthesizing ribosomal RNA per ribosome in the cell. These growth-laws, in turn, reveal two invariants of eukaryotic growth, i.e. quantities predicted to be conserved by Eukarya regardless of growth conditions. The invariants, which are the first of their kind for Eukarya, clarify the coordination of transcription and translation kinetics as required by ribosome biogenesis, and link these kinetic parameters to cellular physiology. We demonstrate application of the relations to the yeast S. cerevisiae and find the predictions to be in good agreement with currently available data. We then outline methods to quantitatively deduce several unknown kinetic and physiological parameters. The analysis is not specific to S. cerevisiae and can be extended to other lower (unicellular) Eukarya when data become available. The relations may also have relevance to certain cancer cells which, like bacteria and yeast, exhibit rapid cell proliferation and ribosome biogenesis.

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Section: Introductionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Graphical Representation Of Boundsmentioning

confidence: 99%

“…Bounds on cellular growth rate from the production of r-protein (orange), 35S-derived rRNA (green), and 5S rRNA (blue). (a) We plot the three bounds [Eqs (21),(23),(24)(20)…”

mentioning

confidence: 99%

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Growth-laws and invariants from ribosome biogenesis in lower Eukarya

Kostinski

Reuveni

2020

Preprint

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TTF1 control of LncRNA synthesis delineates a tumor suppressor pathway directly regulating the ribosomal RNA genes

Sibai,

Tremblay,

Lessard

et al. 2024

Journal Cellular Physiology

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The tumor suppressor p14/19ARF regulates ribosomal RNA (rRNA) synthesis by controlling the nucleolar localization of Transcription Termination Factor 1 (TTF1). However, the role played by TTF1 in regulating the rRNA genes and in potentially controlling growth has remained unclear. We now show that TTF1 expression regulates cell growth by determining the cellular complement of ribosomes. Unexpectedly, it achieves this by acting as a “roadblock” to synthesis of the noncoding LncRNA and pRNA that we show are generated from the “Spacer Promoter” duplications present upstream of the 47S pre‐rRNA promoter on the mouse and human ribosomal RNA genes. Unexpectedly, the endogenous generation of these noncoding RNAs does not induce CpG methylation or gene silencing. Rather, it acts in cis to suppress 47S preinitiation complex formation and hence de novo pre‐rRNA synthesis by a mechanism reminiscent of promoter interference or occlusion. Taken together, our data delineate a pathway from p19ARF to cell growth suppression via the regulation of ribosome biogenesis by noncoding RNAs and validate a key cellular growth law in mammalian cells.

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Ribosomal biogenesis in eukaryotes

Kumar¹

2021

Emerging Concepts in Ribosome Structure, Biogenesis, and Function

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Coupling of Ribosome Synthesis and Translational Capacity with Cell Growth

Cited by 70 publications

References 98 publications

Growth-laws and invariants from ribosome biogenesis in lower Eukarya

Growth-laws and invariants from ribosome biogenesis in lower Eukarya

TTF1 control of LncRNA synthesis delineates a tumor suppressor pathway directly regulating the ribosomal RNA genes

Ribosomal biogenesis in eukaryotes

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