Active Genetics & Molecular Biology Cells, Biochemistry & Physiology

Investigating how cell size alters the RNA-associated proteome and its role in RNA concentration homeostasis

Funder Wellcome Charity-funded
Recipient organisation University of Edinburgh
Funding Not disclosed
Period Oct 2025 — Sept 2028

In plain English

AI plain-English summary

When cells grow too large, their RNA and protein concentrations drop, slowing growth and protein production—and this project aims to find out exactly why that happens. This matters because a fundamental gap in biology is how cell size controls the machinery that makes RNA and proteins. For decades, scientists assumed that ribosome content alone limits cell growth. But this research challenges that idea, pointing instead to a DNA-templated process—likely transcription—as the bottleneck. If the team can show that diluted mRNA, not just fewer ribosomes, is what slows growth in oversized cells, it would overturn a long-standing rule of cell biology. The project is fundamental science with no immediate practical application. It tests a specific mechanism: whether reduced mRNA concentration alters translation initiation and the wider mRNA-binding proteome. The researchers will use UV crosslinking and mass spectrometry to map these changes. If successful, the work could extend the classic “growth laws” of bacteria and yeast to explain how total mRNA levels, not just ribosome numbers, govern cell growth. That deeper understanding might eventually inform how we manipulate cell size in biotechnology or medicine, but for now the goal is simply to correct a basic assumption about how cells work.

View original technical description
Size is an important property for cellular physiology and sets the scale for biosynthesis of RNA and protein. In oversized cells, mRNA, rRNA and protein concentrations decrease, relative protein synthesis and cell growth is reduced. We aim to elucidate the causal links between these size-related effects. These effects are alleviated by increasing cell ploidy, which indicates that a DNA-templated process is limiting for growth. We hypothesise that transcription limits protein synthesis in oversized cells. We test this by sequestering RNA polymerase II in the cytoplasm, which should reduce cellular mRNA to mimick the situation in oversized cells without other size- related confounding effects. A possible scenario where diluted mRNA limits translation is that translation initiation is altered. To test this, I will measure the activity of translation initiation factors and the wider mRNA binding proteome upon dilution of mRNA. This involves crosslinking RNA to protein with UV light and examining the mRNA-binding proteome with mass spectrometry. Our hypotheses partly contradict with a long-standing notion that cell growth is only primarily limited by ribosome content. Therefore, beyond the context of large cell size, this project also informs possible extensions of growth laws to explain the role of total mRNA on cell growth.

View the original record at the funder ↗

Researchers

Huy Le (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

How does cell size influence cellular biosynthesis and function?
Exploring mechanisms underlying cell size-dependent feedback on mRNA decay
Quantitative dissection of protein synthesis initiation at 'omic and single mRNA scales
Investigating RNP granules as centres of novel translational regulation in eukaryotic cells
Why is the bacterial mRNA degradation machinery membrane associated?

Original classification

PhD Studentship (Basic)

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.