poly(UG)-tailed RNAs in genome protection and epigenetic inheritance

Area of Science:

• Genetics
• Molecular Biology
• Epigenetics

Background:

• Mobile genetic elements pose a threat to genome integrity.
• RDE-3 (MUT-2) is a ribonucleotidyltransferase crucial for transposon silencing and RNA interference in C. elegans.
• RDE-3 can add poly(UG) tails to RNAs in heterologous systems.

Purpose of the Study:

• To investigate the role of RDE-3 in its natural context in C. elegans.
• To elucidate the mechanism by which RDE-3 contributes to gene silencing and epigenetic inheritance.

Main Methods:

• Studied RDE-3 activity in C. elegans.
• Analyzed the effect of poly(UG) tails on RNA targeting.
• Investigated the recruitment of RNA-dependent RNA polymerases and siRNA synthesis.

Main Results:

• RDE-3 adds poly(UG) tails to transposon RNAs and RNA interference targets in C. elegans.
• Poly(UG) tails longer than 16 alternating U-G nucleotides confer gene-silencing properties.
• pUG tails recruit RNA-dependent RNA polymerases, leading to siRNA synthesis and transgenerational epigenetic inheritance.

Conclusions:

• A pUG RNA-siRNA silencing loop drives double-stranded RNA-directed transgenerational epigenetic inheritance in the C. elegans germline.
• This mechanism may serve to protect progeny from parasitic genetic elements.