Endonuclease G governs an antiviral RNA surveillance system in budding yeast
- 1University of Toronto
Abstract
Endonuclease G family DNA/RNA nucleases localize to the mitochondrial intermembrane space and prevent escape of mitochondrial DNA to the cytosol or nucleus. While extramitochondrial Endonuclease G also targets nuclear DNA during cell death, RNA regulatory roles of this family remain enigmatic. Here we discover an RNA surveillance system in Saccharomyces cerevisiae governed by Nuc1, the yeast Endonuclease G homolog. This system limits replication of L-A, an RNA mycovirus that endemically infects this organism. Whereas L-A resides in the cytosol, we find that Nuc1's antiviral function requires its mitochondrial intermembrane space localization. To understand Nuc1's indirect antiviral mechanism we investigated its genetic interactions with REX1 and REX2, RNA exonucleases that control 3' end processing of tRNA and rRNA intermediates in the nucleus. We demonstrate that the nuc1{triangleup} antiviral defect is massively amplified by rex1{triangleup} rex2{triangleup} leading to L-A RNA levels that surpass mature rRNAs and overwhelm the cells. NUC1 concurrently controls a pool of mis-processed tRNA and rRNA species that accumulate in rex1{triangleup} rex2{triangleup} mutants. Linking these mis-processed RNAs with L-A control, we show they are significantly reduced in L-A infected cells, suggesting that L-A depletes them to enhance its replication. Our findings identify a previously unrecognized RNA surveillance function of Nuc1 that prevents aberrant rRNA and tRNA species from promoting replication of the L-A mycovirus.
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BibTeX
@misc{gao2026endonuclease,
title = {{Endonuclease G governs an antiviral RNA surveillance system in budding yeast}},
author = {J. Gao and B. Remnant and B. Martyn and M. Chung and J. Li and M. Pickett and S. Chau and M. A. Bayfield and M. D. Meneghini},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.28.762607},
url = {https://www.biorxiv.org/content/10.64898/2026.10.28.762607v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Endonuclease G governs an antiviral RNA surveillance system in budding yeast
AU - J. Gao
AU - B. Remnant
AU - B. Martyn
AU - M. Chung
AU - J. Li
AU - M. Pickett
AU - S. Chau
AU - M. A. Bayfield
AU - M. D. Meneghini
PY - 2026
DA - 2026/10/28
PB - bioRxiv
DO - 10.64898/2026.10.28.762607
UR - https://www.biorxiv.org/content/10.64898/2026.10.28.762607v1
AB - Endonuclease G family DNA/RNA nucleases localize to the mitochondrial intermembrane space and prevent escape of mitochondrial DNA to the cytosol or nucleus. While extramitochondrial Endonuclease G also targets nuclear DNA during cell death, RNA regulatory roles of this family remain enigmatic. Here we discover an RNA surveillance system in Saccharomyces cerevisiae governed by Nuc1, the yeast Endonuclease G homolog. This system limits replication of L-A, an RNA mycovirus that endemically infects this organism. Whereas L-A resides in the cytosol, we find that Nuc1's antiviral function requires its mitochondrial intermembrane space localization. To understand Nuc1's indirect antiviral mechanism we investigated its genetic interactions with REX1 and REX2, RNA exonucleases that control 3' end processing of tRNA and rRNA intermediates in the nucleus. We demonstrate that the nuc1{triangleup} antiviral defect is massively amplified by rex1{triangleup} rex2{triangleup} leading to L-A RNA levels that surpass mature rRNAs and overwhelm the cells. NUC1 concurrently controls a pool of mis-processed tRNA and rRNA species that accumulate in rex1{triangleup} rex2{triangleup} mutants. Linking these mis-processed RNAs with L-A control, we show they are significantly reduced in L-A infected cells, suggesting that L-A depletes them to enhance its replication. Our findings identify a previously unrecognized RNA surveillance function of Nuc1 that prevents aberrant rRNA and tRNA species from promoting replication of the L-A mycovirus.
ER -