Pericentromeric Transcription of Novel Pathogen-Related Human GPS Genes in Cancers is Regulated by C19MC miRNAs, CEBPB, IFN-γ, and IFN-β

Pericentromeric transcription is unique to testis, and oocytes among the normal tissues. However, its regulation in cancer is not well-understood. Here, we discover a novel human, intron-less, coding, pericentromeric GPS gene family in cancer cells, with protein-level homology to microbial proteins from Plasmodium , Staphylococcus, Streptococcus , and Mycobacterium tuberculosis . GPS proteins harbor a conserved FPFP-motif, characteristic of a Mycobacterial protein that hijacks the host ERK-1/2 phosphorylation. We examined the two most expressed GPS family genes ( C6GPS , and C17GPS ) in cancer cells and discovered that the pericentromeric transcription is regulated by interferon-γ and interferon-β, CEBPB-LAP, and antiviral C19MC-miRNAs. Furthermore, GPS mRNAs are suppressed by truncation mutations, and nonsense-mediated decay (NMD). Thus, we discovered a novel pathogen-related GPS gene family in the human genome, and its pericentromeric transcription-regulatory network. This discovery will help to understand the role of GPS pericentromeric transcription in the biology, immunotherapy, and host-pathogen relationships of cancers in the future.