Intrinsically disordered protein PID-2 modulates Z granules and is required for heritable piRNA-induced silencing in...

Area of Science:

• Molecular Biology
• Genetics
• Epigenetics

Background:

• The piRNA (21U RNA) pathway in C. elegans regulates gene expression and germline immortality.
• PRG-1-bound 21U RNAs initiate silencing via RNA-dependent RNA polymerase (RdRP)-synthesized 22G RNAs.
• RNA-induced epigenetic gene silencing (RNAe) is a heritable, PRG-1-independent silencing state, but its establishment and maintenance mechanisms are unknown.

Purpose of the Study:

• To investigate the establishment and maintenance of RNA-induced epigenetic gene silencing (RNAe).
• To identify factors involved in RNAe and germline immortality in C. elegans.
• To elucidate the role of maternally provided 21U RNAs in triggering RNAe.

Main Methods:

• Analysis of RNA-induced epigenetic gene silencing (RNAe) establishment in C. elegans embryos.
• Identification and characterization of proteins involved in RNAe using genetic and biochemical approaches.
• Localization studies of identified proteins and their impact on Z granules and 22G RNA populations.

Main Results:

• Maternally provided 21U RNAs are sufficient to trigger RNAe in embryos.
• PID-2, a protein with intrinsically disordered regions (IDRs), is essential for establishing and maintaining RNAe.
• PID-2 interacts with PID-4 and PID-5, two novel eTudor domain proteins required for germline immortality, perinuclear localization, Z granule regulation, and 22G RNA population balance.

Conclusions:

• Three novel proteins (PID-2, PID-4, PID-5) are identified with critical roles in C. elegans small RNA silencing.
• These proteins are essential for RNA-induced epigenetic gene silencing (RNAe) and germline immortality.
• The findings shed light on the mechanisms underlying heritable gene silencing and germline maintenance.