# An analysis of the regulation and functions of a novel family of membraneless organelles in eukaryotic cells

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2024 · $332,561

## Abstract

The eukaryotic cell is a highly compartmentalized structure that is subdivided into distinct functional areas by the
presence of both membrane-bound and membraneless organelles. These latter compartments have also been
referred to as biomolecular condensates. Although most of these membraneless structures have been identified
only recently, condensate formation has been found to be important for many essential processes in the cell. It
is therefore critical that we develop a thorough understanding of the mechanisms underlying condensate
formation and the nature of their biological activities in the cell.
 We have been addressing these broader issues by studying the biology of one particular condensate,
the Processing body, or P-body. This cytoplasmic granule is highly conserved and contains translationally-
repressed mRNAs and proteins involved in the processing of these transcripts. Our efforts over the past 15 years
have been focused on developing a better understanding of the physiological roles of these granules in the
eukaryotic cell. Studies during the prior grant period furthered this understanding by identifying a potential role
for P-bodies in the regulation of microtubule dynamics. Specifically, we found that a distinct subtype of P-body
granule was induced when the integrity of the microtubule network was disrupted. Moreover, our preliminary
data suggest that these granules may be involved in the specific turnover of the TUB mRNAs that encode tubulin
monomers. The experiments in this proposal are organized into two aims that will (1) define the assembly
pathway for these novel granules and (2) determine how their biological activities are regulated.
 The studies in Aim 1 will specifically test a model proposing that these novel granules form as a result of
select P-body components being recruited to the TUB mRNAs. Interestingly, we have found that this latter decay
in S. cerevisiae exhibits the hallmarks of tubulin autoregulation, a process that has been studied for decades in
mammals. However, the decay machinery responsible for this mRNA turnover has not yet been identified.
Therefore, the studies here could provide resolution for a long-standing question in tubulin biology. In Aim 2, we
will examine how the biological activity of a biomolecular condensate can be controlled by specific constituents
of that structure. We will specifically address a key question concerning the role of P-bodies with respect to
mRNA stability. The primary issue is whether P-bodies are sites of decay or long-term storage for the resident
mRNAs. The experiments here will test a model proposing that P-bodies can alternate between these different
activities and that the transition from one state to the other is controlled by protein constituents of the granule,
like the Hrr25 protein kinase. Finally, we will assess the possibility that the P-body decay machinery is portable
and recruited to select messages that are targeted for degradation. In all, the compl...

## Key facts

- **NIH application ID:** 10892273
- **Project number:** 5R01GM128440-06
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Paul K Herman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $332,561
- **Award type:** 5
- **Project period:** 2018-08-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10892273

## Citation

> US National Institutes of Health, RePORTER application 10892273, An analysis of the regulation and functions of a novel family of membraneless organelles in eukaryotic cells (5R01GM128440-06). Retrieved via AI Analytics 2026-06-15 from https://api.ai-analytics.org/grant/nih/10892273. Licensed CC0.

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