Changes in m6A RNA methylation of goat lung following PPRV infection
Raja Ishaq Nabi Khan,
Manas Ranjan Praharaj,
Waseem Akram Malla,
Neelima Hosamani,
Shikha Saxena,
Bina Mishra,
Kaushal Kishor Rajak,
Muthuchelvan Dhanavelu,
Ashok Kumar Tiwari,
Basavaraj Sajjanar,
Ravi Kumar Gandham,
B.P. Mishra
Affiliations
Raja Ishaq Nabi Khan
Division of Veterinary Biotechnology, ICAR – Indian Veterinary Research Institute, Izatnagar Bareilly, 243122, U.P., India; Center for Advanced Biotechnology and Medicine, Rutgers University, 08854-8021, New Jersey, USA
Manas Ranjan Praharaj
DBT- National Institute of Animal Biotechnology, Hyderabad, 500032, Telangana, India
Waseem Akram Malla
Division of Veterinary Biotechnology, ICAR – Indian Veterinary Research Institute, Izatnagar Bareilly, 243122, U.P., India
Neelima Hosamani
DBT- National Institute of Animal Biotechnology, Hyderabad, 500032, Telangana, India
Shikha Saxena
Division of Veterinary Biotechnology, ICAR – Indian Veterinary Research Institute, Izatnagar Bareilly, 243122, U.P., India
Bina Mishra
Division of Biological Products, ICAR – Indian Veterinary Research Institute, Izatnagar Bareilly, 243122, U.P., India; ICAR – National Bureau of Animal Genetic Resources, Karnal, 132001, Haryana, India
Kaushal Kishor Rajak
Division of Biological Products, ICAR – Indian Veterinary Research Institute, Izatnagar Bareilly, 243122, U.P., India
Muthuchelvan Dhanavelu
Indian Veterinary Research Institute, Bengaluru Campus, 560024, Karnatake, India
Ashok Kumar Tiwari
ICAR – Central Avian Research Institute, Izatnagar Bareilly, 243122, U.P., India
Basavaraj Sajjanar
Division of Veterinary Biotechnology, ICAR – Indian Veterinary Research Institute, Izatnagar Bareilly, 243122, U.P., India; Corresponding author.
Ravi Kumar Gandham
Division of Veterinary Biotechnology, ICAR – Indian Veterinary Research Institute, Izatnagar Bareilly, 243122, U.P., India; ICAR – National Bureau of Animal Genetic Resources, Karnal, 132001, Haryana, India; Corresponding author. Division of Veterinary Biotechnology, ICAR – Indian Veterinary Research Institute, Izatnagar, Bareilly, 243122, U.P., India.
B.P. Mishra
Division of Veterinary Biotechnology, ICAR – Indian Veterinary Research Institute, Izatnagar Bareilly, 243122, U.P., India; ICAR – National Bureau of Animal Genetic Resources, Karnal, 132001, Haryana, India; Corresponding author. Division of Veterinary Biotechnology, ICAR – Indian Veterinary Research Institute, Izatnagar, Bareilly, 243122, U.P., India.
Peste des petits ruminants (PPR) is an acute, highly contagious viral disease of goats and sheep, caused by the Peste des petits ruminants virus (PPRV). Earlier studies suggest the involvement of diverse regulatory mechanisms in PPRV infection. Methylation at N6 of Adenosine called m6A is a type RNA modification that influences various physiological and pathological phenomena. As the lung tissue represents the primary target organ of PPRV, the present study explored the m6A changes and their functional significance in PPRV disease pathogenesis. m6A-seq analysis revealed 1289 m6A peaks to be significantly altered in PPRV infected lung in comparison to normal lung, out of which 975 m6A peaks were hypomethylated and 314 peaks were hypermethylated. Importantly, hypomethylated genes were enriched in Interleukin-4 and Interleukin-13 signaling and various processes associated with extracellular matrix organization. Further, of the 843 differentially m6A-containing cellular transcripts, 282 transcripts were also found to be differentially expressed. Functional analysis revealed that these 282 transcripts are significantly enriched in signaling by Interleukins, extracellular matrix organization, cytokine signaling in the immune system, signaling by receptor tyrosine kinases, and Toll-like Receptor Cascades. We also found m6A reader HNRNPC and the core component of methyltransferase complex METTL14 to be highly upregulated than the m6A readers – HNRNPA2B1 and YTHDF1 at the transcriptome level. These findings suggest that alteration in the m6A landscape following PPRV is implicated in diverse processes including Interleukin signaling.
