# ERK mediated control of Dicer and Drosha in C. elegans

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2020 · $379,947

## Abstract

PROJECT SUMMARY
In human females, meiosis I is completed prior to birth. The oocyte then arrests at meiosis II until puberty
whereupon it undergoes maturation and ovulation and is ready to be fertilized. Upon fertilization, embryonic
development ensues. At the end of meiosis I oocytes accumulate a stockpile of mRNAs that are (a) necessary
for oocyte growth (“oogenic RNAs”), and (b) that are contributed maternally to the embryo (“maternal RNAs”).
Once early embryonic development is complete however, degradation of the maternal RNAs is critical for
reprogramming gene expression to transition to a totipotent embryo and enable embryonic genome activation.
Errors in generation and/or protection of the oogenic and maternal RNAs grossly affect oogenesis; in contrast
errors in the degradation of oogenic and maternal RNAs in the embryo affect embryonic development. Taken
together, such errors are a major cause of human infertility and birth defects. Molecular mechanisms that
regulate oogenic and maternal RNA generation and timely degradation are thus critical to understand, and
remain to be fully elucidated. Using C. elegans meiosis I oocytes as our model system we identified that the
nutritionally regulated RAS/ERK signaling pathway directly controls Dicer and Drosha, small RNA biogenesis
enzymes, during meiosis I, to mediate normal oogenesis. Additionally, Dicer needs to be dephosphorylated to
enable normal embryonic progression. We propose that progression of oogenesis is enabled through
suppression of small RNAs, likely because oogenic RNAs are protected from degradation for translational
regulation. Conversely, embryonic development likely ensues because of degradation of the maternal RNAs
upon activation of the small RNAs. Together, these observations lead to the model that signal-induced
regulation of Dicer and Drosha coordinates the generation and protection of maternal RNAs during oogenesis
with their timely degradation in the embryo, with direct implications to understanding both infertility and birth
defects.

## Key facts

- **NIH application ID:** 9982338
- **Project number:** 5R01GM098200-09
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Swathi Arur
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $379,947
- **Award type:** 5
- **Project period:** 2011-09-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982338

## Citation

> US National Institutes of Health, RePORTER application 9982338, ERK mediated control of Dicer and Drosha in C. elegans (5R01GM098200-09). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/9982338. Licensed CC0.

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