Cited by 6RNA Interference and Gene DeliveryChromosomal and Genetic VariationsEpigenetics and DNA Methylation

Intergenerational transport of double-stranded RNA in C. elegans can limit heritable epigenetic changes

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Shugarts Devanapally, Nathan M, Sathya, Aishwarya, Yi, Andrew L, Chan, Winnie M, Marre, Julia A, Jose, Antony M·2025·eLife

Published version of a preprint

Abstract

RNAs in circulation carry sequence-specific regulatory information between cells in plant, animal, and host-pathogen systems. Such RNA can cross generational boundaries, as evidenced by somatic double-stranded RNA (dsRNA) in the nematode Caenorhabditis elegans silencing genes of matching sequence in progeny. Here we dissect the intergenerational path taken by dsRNA from parental circulation and discover that cytosolic import through the dsRNA importer SID-1 in the parental germline and/or developing progeny varies with developmental time and dsRNA substrates. Loss of SID-1 enhances initiation of heritable RNA silencing within the germline and causes changes in the expression of the s id-1 - d ependent g ene sdg-1 that last for more than 100 generations after restoration of SID-1. The SDG-1 protein is enriched in perinuclear germ granules required for heritable RNA silencing but is expressed from a retrotransposon targeted by such silencing. This auto-inhibitory loop suggests how retrotransposons could persist by hosting genes that regulate their own silencing.

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Authors
Shugarts Devanapally, N. M., Sathya, A., Yi, A. L., Chan, W. M., Marre, J. A., & Jose, A. M.
Affiliations
  • Department of Cell Biology and Molecular Genetics, University of Maryland
  • University of Maryland, College Park (US)
Corresponding author
Jose, Antony M
Venue
eLife
Published
2025-02-04
Volume
13
ISSN
2050-084X (ISSN-L)
OpenAlex
W4407139509
Cited by
6
References
117
Citations by year
2026: 4 · 2025: 1 · 2024: 1
Type
posted content
Language
en
Open access
Locations
  • eLife (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institute of General Medical Sciences (R01GM111457, R01GM124356)
  • University of Maryland (UMD CMNS Dean's Matching Award for "Training Program in Cell and Molecular Biology" T32GM080201)
  • National Science Foundation (2120895)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
double-stranded RNA, SID-1, SDG 1, germ granules, retrotransposons, epigenetic inheritance, germline, Caenorhabditis elegans
MeSH terms
Animals, Membrane Proteins, RNA, Double-Stranded, Caenorhabditis elegans, Retroelements, Caenorhabditis elegans Proteins, RNA Interference, Epigenesis, Genetic

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