Abstract

Pre- and post-transcriptional modifications of gene expression are emerging as foci of disease studies, with some studies revealing the importance of non-coding transcripts, like long non-coding RNAs (lncRNAs) and microRNAs (miRNAs). We hypothesize that transcription factors (TFs), lncRNAs and miRNAs modulate immune response in bovine mastitis and could potentially serve as disease biomarkers and/or drug targets. With computational analyses, we identified candidate genes potentially regulated by miRNAs and lncRNAs base pair complementation and thermodynamic stability of binding regions. Remarkably, we found six miRNAs, two being bta-miR-223 and bta-miR-24-3p, to bind to several targets. LncRNAs NONBTAT027932.1 and XR_003029725.1, were identified to target several genes. Functional and pathway analyses revealed lipopolysaccharide-mediated signaling pathway, regulation of chemokine (C-X-C motif) ligand 2 production and regulation of IL-23 production among others. The overarching interactome deserves further in vitro/in vivo explication for specific molecular regulatory mechanisms during bovine mastitis immune response and could lay the foundation for development of disease markers and therapeutic intervention.

Highlights

  • Bovine mastitis, caused by a variety of organisms, including Staphylococci, Streptococci, and Enterobacteria, is a mammary gland infection posing a great threat to the dairy industry, and is the costliest disease affecting cattle, due to its impact on the quality and quantity of milk p­ roduction[1,2]

  • Dataset of candidate genes associated with immune response to bovine mastitis

  • The present study provides computational evidence that miRNA, long non-coding RNAs (lncRNAs), and transcription factors (TFs) could regulate the host immune response to bovine mastitis

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Summary

Introduction

Bovine mastitis, caused by a variety of organisms, including Staphylococci, Streptococci, and Enterobacteria, is a mammary gland infection posing a great threat to the dairy industry, and is the costliest disease affecting cattle, due to its impact on the quality and quantity of milk p­ roduction[1,2]. LncRNAs are long non-coding RNA transcripts, harboring a 5′ cap and 3′ poly (A) tail but no functional open reading frame, and as such cannot encode p­ roteins[8,9]. This heterogeneous class of RNAs can modulate gene expression and protein synthesis at the transcriptional and post-transcriptional levels via complementary base ­pairing[10]. We propose the need to understand the crosstalk between miRNA, lncRNA and TFs, and the role they play in regulating genes associated with bovine mastitis, including the possibility of translation to drug treatment or disease prevention therapies. If a regulatory element plays a key role in disease pathogenesis or in the immune response, this may be an ideal drug target for treatment

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