Small RNA-mediated genomic silencing promotes telomere stability in the absence of telomerase in C. elegans
- 1University of North Carolina at Chapel Hill
Abstract
We previously found that small RNAs with perfect homology to (TTAGGC)n telomere repeats are very rare. Here we use long read sequencing to reveal that most N2 wild type C. elegans strains have few telomere mutations at 5 prime ends of telomeres, where the telomeric lncRNA TERRA is transcribed. Therefore, telomere mutations cannot explain the absence of perfect small RNAs to (TTAGGC)n telomere repeats. We show that the heterochromatin mark H3K9me2 is enriched at C. elegans sub-telomeres and that the HP1 protein HPL-2 that binds H3K9me2 promotes telomere stability in the absence of telomerase. Small RNA silencing can promote H3K9 methylation, and telomere stability in the absence of telomerase requires germ granule proteins MUT-7 and MUT-14 that promote small RNA biogenesis and also WAGO-1 and HRDE-1 Argonaute proteins that bind subtelomeric small RNAs. Loss of telomerase induced biogenesis of small RNAs from the subtelomeric 5 prime end of the telomeric lncRNA TERRA but not from telomere repeats of TERRA. Loss of both telomerase and small RNA-mediated genome silencing induced TERRA expression, telomere damage and accelerated sterility. We propose that small RNA-mediated heterochromatin formation and telomerase function redundantly to repress a form of telomeric DNA damage that is coupled to TERRA expression and subtelomeric small RNA biogenesis. However, telomere repeats of TERRA strongly resisted RNA-dependent RNA polymerase activity in telomerase mutants, revealing an exceptional quality of telomere repeat RNA.
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BibTeX
@misc{lu2026small,
title = {{Small RNA-mediated genomic silencing promotes telomere stability in the absence of telomerase in C. elegans}},
author = {L. Lu and A. Bhattarai and C. Longtine and S. Frenk and M. Garrison and J. S. Lee and E. H. Lister-Shimauchi and S. Ahmed},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.1101/292722},
url = {https://www.biorxiv.org/content/10.1101/292722v6},
note = {CC BY},
}
RIS
TY - UNPB
TI - Small RNA-mediated genomic silencing promotes telomere stability in the absence of telomerase in C. elegans
AU - L. Lu
AU - A. Bhattarai
AU - C. Longtine
AU - S. Frenk
AU - M. Garrison
AU - J. S. Lee
AU - E. H. Lister-Shimauchi
AU - S. Ahmed
PY - 2026
DA - 2026/11/06
PB - bioRxiv
DO - 10.1101/292722
UR - https://www.biorxiv.org/content/10.1101/292722v6
AB - We previously found that small RNAs with perfect homology to (TTAGGC)n telomere repeats are very rare. Here we use long read sequencing to reveal that most N2 wild type C. elegans strains have few telomere mutations at 5 prime ends of telomeres, where the telomeric lncRNA TERRA is transcribed. Therefore, telomere mutations cannot explain the absence of perfect small RNAs to (TTAGGC)n telomere repeats. We show that the heterochromatin mark H3K9me2 is enriched at C. elegans sub-telomeres and that the HP1 protein HPL-2 that binds H3K9me2 promotes telomere stability in the absence of telomerase. Small RNA silencing can promote H3K9 methylation, and telomere stability in the absence of telomerase requires germ granule proteins MUT-7 and MUT-14 that promote small RNA biogenesis and also WAGO-1 and HRDE-1 Argonaute proteins that bind subtelomeric small RNAs. Loss of telomerase induced biogenesis of small RNAs from the subtelomeric 5 prime end of the telomeric lncRNA TERRA but not from telomere repeats of TERRA. Loss of both telomerase and small RNA-mediated genome silencing induced TERRA expression, telomere damage and accelerated sterility. We propose that small RNA-mediated heterochromatin formation and telomerase function redundantly to repress a form of telomeric DNA damage that is coupled to TERRA expression and subtelomeric small RNA biogenesis. However, telomere repeats of TERRA strongly resisted RNA-dependent RNA polymerase activity in telomerase mutants, revealing an exceptional quality of telomere repeat RNA.
ER -