Functional Study of the Retrotransposon-Derived Human PEG10 Protease

• Published in: International journal of molecular sciences Vol. 21; no. 7; p. 2424
• Main Authors: Golda, Mária, Mótyán, János András, Mahdi, Mohamed, Tőzsér, József
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 31.03.2020; MDPI AG
• Subjects: Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; Aspartic Acid Endopeptidases - genetics; Cell Proliferation; Cell Survival; cell viability; cis protease activity; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Frameshift Mutation; HaCaT Cells; HEK293 Cells; Humans; paternally expressed gene 10; PEG10; Peptide Hydrolases - genetics; Peptide Hydrolases - metabolism; Protein Isoforms; Reading Frames; Recombinant Proteins; Retroelements - physiology; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Sequence Alignment; Transfection; ubiquitination; cis protease activity; protease; cell viability; homology modeling; cell proliferation; ubiquitination; PEG10; paternally expressed gene 10; retrotransposon; retroviral-like protease
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21072424

Paternally expressed gene 10 (PEG10) is a human retrotransposon-derived imprinted gene. The mRNA of encodes two protein isoforms: the Gag-like protein (RF1 ) is coded by reading frame 1, while the Gag-Pol-like polyprotein (RF1/RF2 ) is coded by reading frames 1 and 2. The proteins are translated by a typical retroviral frameshift mechanism. The protease (PR) domain of RF2 contains an -Asp-Ser-Gly- sequence, which corresponds to the consensus -Asp-Ser/Thr-Gly- active-site motif of retroviral aspartic proteases. The function of the aspartic protease domain of RF2 remains unclear. To elucidate the function of PEG10 protease (PR ), we designed a frameshift mutant ( RF1/RF2 ) for comparison with the RF1/RF2 form. To study the effects of PR on cellular proliferation and viability, mammalian HEK293T and HaCaT cells were transfected with plasmids coding for either RF1/RF2 , the frameshift mutant ( RF1/RF2 ), or a PR active-site (D370A) mutant RF1/RF2 . Our results indicate that RF1/RF2 overexpression results in increased cellular proliferation. Remarkably, transfection with RF1/RF2 had a detrimental effect on cell viability. We hypothesize that PR plays an important role in the function of this retroviral remnant, mediating the proliferation of cells and possibly implicating it in the inhibition of apoptosis.