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

doi:10.1016/j.heliyon.2023.e19358

Changes in m⁶A RNA methylation of goat lung following PPRV infection

Heliyon. 2023 Aug 22;9(9):e19358. doi: 10.1016/j.heliyon.2023.e19358. eCollection 2023 Sep.

Authors

Raja Ishaq Nabi Khan^{1

2}, Manas Ranjan Praharaj^{3

4}, Waseem Akram Malla¹, Neelima Hosamani³, Shikha Saxena¹, Bina Mishra^{5

6}, Kaushal Kishor Rajak⁵, Muthuchelvan Dhanavelu⁷, Ashok Kumar Tiwari⁸, Basavaraj Sajjanar¹, Ravi Kumar Gandham^{1

6}, B P Mishra^{1

6}

Affiliations

¹ Division of Veterinary Biotechnology, ICAR - Indian Veterinary Research Institute, Izatnagar Bareilly, 243122, U.P., India.
² Center for Advanced Biotechnology and Medicine, Rutgers University, 08854-8021, New Jersey, USA.
³ DBT- National Institute of Animal Biotechnology, Hyderabad, 500032, Telangana, India.
⁴ DBT-Regional Centre for Biotechnology (RCB), Faridabad 121001, Haryana, India.
⁵ Division of Biological Products, ICAR - Indian Veterinary Research Institute, Izatnagar Bareilly, 243122, U.P., India.
⁶ ICAR - National Bureau of Animal Genetic Resources, Karnal, 132001, Haryana, India.
⁷ Indian Veterinary Research Institute, Bengaluru Campus, 560024, Karnatake, India.
⁸ ICAR - Central Avian Research Institute, Izatnagar Bareilly, 243122, U.P., India.

Abstract

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.

Keywords: Epitranscriptomics; Peste des petits ruminants virus; RNA methylation; m6A.