# mRNA regulation, localization, and dynamics in C. elegans embryogenesis

> **NIH NIH R35** · COLORADO STATE UNIVERSITY · 2023 · $390,911

## Abstract

PROJECT SUMMARY/ABSTRACT:
 Cells of the Caenorhabditis elegans early embryo diversify their mRNA content even in the absence of
de novo transcription. This remarkable feat has given my lab a unique vantage from which to study post-
transcriptional regulation. Surprisingly, we found that many mRNA transcripts which exhibit cell-specific
patterning also localize to discrete subcellular structures such as biomolecular condensates or membranes. My
lab aims to understand how subcellular mRNA patterning arises mechanistically, how it functionally
links to protein production, and how it impacts development. Recent advances have identified 190,000
localized mRNA transcripts found at 44 subcellular locales across 65 species (RNALocate Database). These
transcripts include many that impact human neurobiology and whose mislocalization is associated with
disease. Many more represent mRNAs that accumulate at cellular regions through unknown mechanisms and
for undefined purposes, underscoring the potential for new discoveries that we aim to make.
 In the first funding phase, my group determined mechanisms that localize mRNAs to P granules
(cytoplasmic condensates important for germline development and fertility). Transcripts that associate with P
granules undergo either temporary sequestration or permanent decay. In the next phase, we will address
the signals, mechanisms, and dynamics that distinguish P granule-associated mRNA sequestration
from decay. Specifically, we will differentiate between competing models explaining how the conserved
transcript nos-2 (nanos) exits P granules and initiates its translation to ensure fertility.
 Previously, we identified several mRNA transcripts that localize to membranes along with the proteins
they encode, a finding echoed in other organisms. Among these were erm-1 a member of a conserved family
of cytoskeletal membrane linker proteins that impacts cell shape and cancer. We found that erm-1’s mRNA
localization is translation-dependent. Next, we will address the mechanisms and principles explaining
how and why complexes of translating erm-1 move to membranes. We will also use genomics to
characterize the membrane-enriched transcriptome to better understand localized translation at membranes.
 Maternal mRNA transcripts undergo decay in early embryos often creating cell-specific patterns that
direct cell differentiation. In the first funding cycle, we demonstrated a requirement for the RNA binding protein
SPN-4 in the clearance and cell-specificity of some transcripts. In the next phase, we will determine how
SPN-4 shapes the transcriptome and works in concert with other mechanisms of mRNA clearance.
 The sum of these projects will be to create an overarching research program aimed at
describing how mRNA transcripts organize spatially within the cell and how that organization can
impact gene expression and embryogenesis.

## Key facts

- **NIH application ID:** 10674715
- **Project number:** 5R35GM124877-07
- **Recipient organization:** COLORADO STATE UNIVERSITY
- **Principal Investigator:** Erin Osborne Nishimura
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $390,911
- **Award type:** 5
- **Project period:** 2017-08-18 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10674715

## Citation

> US National Institutes of Health, RePORTER application 10674715, mRNA regulation, localization, and dynamics in C. elegans embryogenesis (5R35GM124877-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10674715. Licensed CC0.

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