PML and PML-like exonucleases restrict retrotransposons in jawed vertebrates

Area of Science:

• Genetics
• Molecular Biology
• Evolutionary Biology

Background:

• The promyelocytic leukemia (PML) gene is known for forming nuclear bodies in mammals.
• Genome stability is crucial and can be threatened by mobile genetic elements like LINE-1 (L1).

Purpose of the Study:

• To investigate the role of PML and novel PML-like DEDDh exonucleases in restricting LINE-1 retrotransposition across jawed vertebrates.
• To understand the evolutionary trajectory and functional conservation of PML and related exonucleases in genome defense.

Main Methods:

• Comparative genomics and molecular evolution analyses of PML and TREX1 homologs.
• Functional assays in cellulo to assess the restriction of L1 retrotransposition.
• Subcellular localization studies of PML and PML-like proteins.

Main Results:

• Spotted gar PML and fish Plex9 proteins function as cytoplasmic DEDDh exonucleases that suppress L1 retrotransposition.
• PML proteins in amniotes exhibit dual localization (cytoplasm and nuclear bodies) and retain cytoplasmic L1 restriction.
• Gar PML and zebrafish Plex9 exhibit convergent evolution with TREX1 in suppressing L1 and can rescue TREX1 knockout phenotypes.

Conclusions:

• PML initially evolved as a cytoplasmic retroelement suppressor, a function maintained in amniotes alongside its role in nuclear body formation.
• PML-like exonucleases, such as Plex9, represent a conserved defense mechanism against L1 retrotransposition in vertebrates.
• Understanding these ancient defense mechanisms is key to comprehending genome stability maintenance throughout vertebrate evolution.