Pericentromeric Transcription of Novel Pathogen-Related Human GPS Genes in Cancers is Regulated by C19MC miRNAs,...

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.