Minor intron-containing genes as an ancient backbone for viral infection?

Stefan Wuchty; Alisa K White; Anouk M Olthof; Kyle Drake; Adam J Hume; Judith Olejnik; Vanessa Aguiar-Pulido; Elke Mühlberger; Rahul N Kanadia

doi:10.1093/pnasnexus/pgad479

Minor intron-containing genes as an ancient backbone for viral infection?

PNAS Nexus. 2024 Jan 18;3(1):pgad479. doi: 10.1093/pnasnexus/pgad479. eCollection 2024 Jan.

Authors

Stefan Wuchty^{1

2

3

4}, Alisa K White⁵, Anouk M Olthof⁵, Kyle Drake⁵, Adam J Hume^{6

7

8}, Judith Olejnik^{6

7}, Vanessa Aguiar-Pulido¹, Elke Mühlberger^{6

7}, Rahul N Kanadia^{5

9}

Affiliations

¹ Department of Computer Science, University of Miami, Coral Gables, FL 33146, USA.
² Department of Biology, University of Miami, Coral Gables, FL 33146, USA.
³ Institute of Data Science and Computing, University of Miami, Coral Gables, FL 33146, USA.
⁴ Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33134, USA.
⁵ Physiology and Neurobiology Department, University of Connecticut, Storrs, CT 06269, USA.
⁶ Department of Virology, Immunology and Microbiology, Boston University Chobanian and Avedisian School of Medicine, Boston, MA 02118, USA.
⁷ National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA 02118, USA.
⁸ Center for Emerging Infectious Diseases Policy and Research, Boston University, Boston, MA 02118, USA.
⁹ Institute for Systems Genomics, University of Connecticut, Storrs, CT 06269, USA.

Abstract

Minor intron-containing genes (MIGs) account for <2% of all human protein-coding genes and are uniquely dependent on the minor spliceosome for proper excision. Despite their low numbers, we surprisingly found a significant enrichment of MIG-encoded proteins (MIG-Ps) in protein-protein interactomes and host factors of positive-sense RNA viruses, including SARS-CoV-1, SARS-CoV-2, MERS coronavirus, and Zika virus. Similarly, we observed a significant enrichment of MIG-Ps in the interactomes and sets of host factors of negative-sense RNA viruses such as Ebola virus, influenza A virus, and the retrovirus HIV-1. We also found an enrichment of MIG-Ps in double-stranded DNA viruses such as Epstein-Barr virus, human papillomavirus, and herpes simplex viruses. In general, MIG-Ps were highly connected and placed in central positions in a network of human-host protein interactions. Moreover, MIG-Ps that interact with viral proteins were enriched with essential genes. We also provide evidence that viral proteins interact with ancestral MIGs that date back to unicellular organisms and are mainly involved in basic cellular functions such as cell cycle, cell division, and signal transduction. Our results suggest that MIG-Ps form a stable, evolutionarily conserved backbone that viruses putatively tap to invade and propagate in human host cells.

Keywords: minor introns; viral infections.