The gag-like gene RTL8 antagonizes PEG10-mediated virus like particles

Area of Science:

• Genetics
• Molecular Biology
• Cell Biology

Background:

• PEG10 (Paternally Expressed Gene 10) is a retroelement-derived gene crucial for mammalian placentation and implicated in neurological disorders.
• PEG10 proteins assemble into virus-like particles (VLPs), essential for their biological functions.
• The precise regulation of PEG10 VLP formation and release remains incompletely understood.

Purpose of the Study:

• To investigate the regulatory mechanisms governing PEG10 VLP formation and release in human cells.
• To elucidate the role of the related Mart gene RTL8 in PEG10 VLP biology.
• To understand the functional implications of the interaction between PEG10 and RTL8.

Main Methods:

• Co-expression of PEG10 and RTL8 in human cells.
• Purification of VLPs using iodixanol ultracentrifugation.
• Analysis of VLP abundance and intracellular protein levels via biochemical assays.
• Investigation of protein-protein interactions using binding assays.

Main Results:

• RTL8, a truncated form of PEG10, is incorporated into PEG10-derived VLPs.
• Co-expression of RTL8 with PEG10 reduces VLP abundance while increasing intracellular PEG10 levels.
• RTL8 binds to the N-terminal capsid domain of PEG10, inhibiting VLP formation or release.
• RTL8 modulates PEG10 VLP abundance in naturally producing cells and is co-expressed with PEG10 in various tissues, including the brain.

Conclusions:

• A novel antagonistic relationship exists between the retroelement-derived genes PEG10 and RTL8.
• RTL8 acts as a negative regulator of PEG10 VLP formation/release, influencing PEG10's biological roles.
• These findings provide new insights into the regulation of PEG10 and its implications in reproduction and neurological disease.