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Mechanisms of cellular mRNA transcript homeostasis

Journal

TRENDS IN CELL BIOLOGY
Volume 32, Issue 8, Pages 655-668

Publisher

CELL PRESS
DOI: 10.1016/j.tcb.2022.05.003

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Categories

Funding

  1. EMBO long-term fellowship [ALTF1175-2016]
  2. Human Frontier Science Program (HFSP) long-term fellowship [LT000238/2017-L]
  3. University of New South Wales
  4. European Research Council [ERC-2019-AdG-885579]
  5. Swiss National Science Foundation (SNSF) [310030_192622]
  6. University of Zurich
  7. Swiss National Science Foundation (SNF) [310030_192622] Funding Source: Swiss National Science Foundation (SNF)

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The relationship between mRNA transcript abundance and cell size, as well as the regulation of RNA polymerase II activity and abundance, are discussed in this article. Feedback mechanisms that adjust mRNA synthesis rates, nuclear export, and degradation are also identified, allowing cells to compensate for changes in one aspect by adjusting others. Researchers are integrating findings from different fields to understand the mechanisms underlying transcript homeostasis and its connection to other aspects of the cellular phenotype.
For most genes, mRNA transcript abundance scales with cell size to ensure a constant concentration. Scaling of mRNA synthesis rates with cell size plays an important role, with regulation of the activity and abundance of RNA polymerase II (Pol II) now emerging as a key point of control. However, there is also considerable evidence for feedback mechanisms that kinetically couple the rates of mRNA synthesis, nuclear export, and degradation to allow cells to compensate for changes in one by adjusting the others. Researchers are beginning to integrate results from these different fields to reveal the mechanisms underlying transcript homeostasis. This will be crucial for moving beyond our current understanding of relative gene expression towards an appreciation of how absolute transcript levels are linked to other aspects of the cellular phenotype.

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