Two SID-1-dependent genes sensitive to heritable epigenetic changes can also impact reproduction.

Area of Science:

• Epigenetics and Transgenerational Inheritance
• Molecular Biology
• Genetics

Background:

• Extracellular double-stranded RNA (dsRNA) import into the germline can induce heritable changes in gene expression.
• The transmembrane protein SID-1 facilitates dsRNA entry into the cytosol, and its absence leads to persistent gene expression alterations.
• The specific roles of SID-1-dependent genes (SDGs) in transgenerational regulation remain largely uncharacterized.

Purpose of the Study:

• To identify and analyze additional SID-1-dependent genes (SDGs) involved in transgenerational epigenetic inheritance.
• To investigate the function and localization of two germline-expressed SDGs, SDG-1 and SDG-2, in C. elegans.
• To explore the reproductive consequences and potential mechanisms of SDG-1 and SDG-2 regulation.

Main Methods:

• Expanded identification of SID-1-dependent genes (SDGs).
• Generation and analysis of endogenous SDG-1::mCherry and SDG-2::mCherry fusion proteins in C. elegans.
• Phenotypic analysis of knockout mutants (sdg-1, sdg-2) and fusion protein strains, including brood size, progeny count, and germline morphology.
• Subcellular localization studies of SDG-1::mCherry and SDG-2::mCherry proteins.

Main Results:

• Deletion of sdg-1 or sdg-2 reduced brood size in specific lineages.
• SDG-1::mCherry localized to nuclei, germ granules, and microtubules, and its presence affected progeny count and germline morphology.
• Transgenerational effects of SDG-1::mCherry were observed in siblings lacking the sdg-1 gene.
• SDG-2::mCherry was detected in the cytoplasm and nucleus, and its structure suggests interaction with TRA-1, a regulator of spermatogenesis.
• Both SDG-1 and SDG-2 appear to influence reproductive capacity.

Conclusions:

• SDG-1 and SDG-2 play significant roles in C. elegans reproduction and germline integrity.
• The observed phenotypes and localization patterns suggest complex regulatory functions for SDG-1 and SDG-2.
• SID-1-mediated import of extracellular dsRNA or other SID-1 functions regulating SDGs may modulate the long-term impacts of ancestral epigenetic changes.