# Control of C. elegans Lineage by Heterochronic Genes

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $636,718

## Abstract

Project Summary/Abstract:
We have identified genes that act in the maturation or presentation of siRNAs that mediate antiviral defense
in C. elegans. We propose to discern how the siRNAs and other small RNAs may be edited analogous to
the ancient editing of wobble base pairs in the anticodon loop of many tRNAs, to allow this system to
anticipate infection with viruses related to virus infections recorded in the genome. Our saturation genetic
analysis of these antiviral pathways has revealed new possibilities for how the genomic record of past viral
infections via RNA editing and DNA recombination between repetitive elements can anticipate future viral
variation. This is equivalent to wobble base pairing between tRNA and codons, which is mediated by very
ancient RNA modification pathways. Thus the modern RNA world, which is heavily populated by parasitic
RNA viruses such as Covid-19, may depend on ancient RNA editing. Our hypothesis that synMuv genes
mediate gene amplification in the intestine and other tissues to produce substrates for unequal crossing over
is very unorthodox, but intersects nicely with the translocations so common in tumor biology. It could be
transformative for cancer biology.

## Key facts

- **NIH application ID:** 10209198
- **Project number:** 2R01GM044619-29
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** GARY B RUVKUN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $636,718
- **Award type:** 2
- **Project period:** 1991-05-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10209198

## Citation

> US National Institutes of Health, RePORTER application 10209198, Control of C. elegans Lineage by Heterochronic Genes (2R01GM044619-29). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10209198. Licensed CC0.

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