Genome-wide long non-coding RNA expression profile and its regulatory role in the ileocecal valve from Mycobacterium avium subsp. paratuberculosis-infected cattle

Bovine paratuberculosis (PTB) is a chronic enteritis caused by Mycobacterium avium subsp. paratuberculosis (MAP), which results in significant economic losses to the dairy industry worldwide. Long non-coding RNAs (lncRNAs) play a crucial role in regulating the host immune response due to their inter...

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Main Authors: Gerard Badia-Bringué, Victoria Asselstine, Ángela Cánovas, Marta Alonso-Hearn
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Veterinary Science
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Online Access:https://www.frontiersin.org/articles/10.3389/fvets.2025.1601267/full
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author Gerard Badia-Bringué
Victoria Asselstine
Ángela Cánovas
Marta Alonso-Hearn
author_facet Gerard Badia-Bringué
Victoria Asselstine
Ángela Cánovas
Marta Alonso-Hearn
author_sort Gerard Badia-Bringué
collection DOAJ
description Bovine paratuberculosis (PTB) is a chronic enteritis caused by Mycobacterium avium subsp. paratuberculosis (MAP), which results in significant economic losses to the dairy industry worldwide. Long non-coding RNAs (lncRNAs) play a crucial role in regulating the host immune response due to their interaction with transcripts in proximity. However, their annotation in cattle remains limited, and their role in cattle naturally infected with MAP has not been fully explored. In this study, lncRNAs were identified in the transcriptome of ileocecal valve samples from control cows without lesions (N = 4) and with PTB-associated focal (N = 5) and diffuse (N = 5) lesions in intestinal tissues using RNA sequencing. The raw reads were uploaded into the CLC Bio Genomics Workbench, and the trimmed reads were mapped to the Bos taurus ARS_UCD1.2.109 reference genome using the Large Gap Read Mapping tool. The resulting annotation allowed the identification of 1,434 LncRNAs, 899 of which were novel, using the FlExible Extraction of LncRNA pipeline. LncRNA differential expression (DE) analysis performed with DESeq2 allowed the identification of 1, 6, and 2 DE lncRNAs in the comparisons of cows with focal lesions versus (vs) controls, diffuse lesions vs. controls, and diffuse vs. focal lesions, respectively. Best lncRNA partner analysis identified expression correlations between the lncRNA1086.1, lncRNA ENSBTAG00000050406, and lncRNA_2340.1, and the Inactive Phosphatidylinositol 3-Phosphatase 9 (MTMR9), GM Domain Family member B (RGMB), and the homeobox A6 (HOXA6), respectively. The MTMR9 negatively regulates apoptosis, the RGMB positively regulates IL-6 expression, and the HOXA6 regulates cell differentiation and inflammation. The results of the quantitative trait locus (QTL) enrichment analysis showed that the DE lncRNAs were located in genomic regions previously associated with clinical mastitis, HDL cholesterol, bovine tuberculosis, paratuberculosis, and bovine leukosis susceptibility. The identified DE lncRNAs could allow the development of novel PTB diagnostic tools and have potential applications in breeding strategies for PTB-resistant cattle.
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spelling doaj-art-4fcea7b4875d43f8b1357c3d06a3cff32025-08-20T03:24:48ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692025-06-011210.3389/fvets.2025.16012671601267Genome-wide long non-coding RNA expression profile and its regulatory role in the ileocecal valve from Mycobacterium avium subsp. paratuberculosis-infected cattleGerard Badia-Bringué0Victoria Asselstine1Ángela Cánovas2Marta Alonso-Hearn3Department of Animal Health, NEIKER-Basque Institute of Agricultural Research and Development, Basque Research and Technology Alliance (BRTA), Derio, SpainDepartment of Animal Biosciences, Center for Genetic Improvement of Livestock, University of Guelph, Guelph, ON, CanadaDepartment of Animal Biosciences, Center for Genetic Improvement of Livestock, University of Guelph, Guelph, ON, CanadaDepartment of Animal Health, NEIKER-Basque Institute of Agricultural Research and Development, Basque Research and Technology Alliance (BRTA), Derio, SpainBovine paratuberculosis (PTB) is a chronic enteritis caused by Mycobacterium avium subsp. paratuberculosis (MAP), which results in significant economic losses to the dairy industry worldwide. Long non-coding RNAs (lncRNAs) play a crucial role in regulating the host immune response due to their interaction with transcripts in proximity. However, their annotation in cattle remains limited, and their role in cattle naturally infected with MAP has not been fully explored. In this study, lncRNAs were identified in the transcriptome of ileocecal valve samples from control cows without lesions (N = 4) and with PTB-associated focal (N = 5) and diffuse (N = 5) lesions in intestinal tissues using RNA sequencing. The raw reads were uploaded into the CLC Bio Genomics Workbench, and the trimmed reads were mapped to the Bos taurus ARS_UCD1.2.109 reference genome using the Large Gap Read Mapping tool. The resulting annotation allowed the identification of 1,434 LncRNAs, 899 of which were novel, using the FlExible Extraction of LncRNA pipeline. LncRNA differential expression (DE) analysis performed with DESeq2 allowed the identification of 1, 6, and 2 DE lncRNAs in the comparisons of cows with focal lesions versus (vs) controls, diffuse lesions vs. controls, and diffuse vs. focal lesions, respectively. Best lncRNA partner analysis identified expression correlations between the lncRNA1086.1, lncRNA ENSBTAG00000050406, and lncRNA_2340.1, and the Inactive Phosphatidylinositol 3-Phosphatase 9 (MTMR9), GM Domain Family member B (RGMB), and the homeobox A6 (HOXA6), respectively. The MTMR9 negatively regulates apoptosis, the RGMB positively regulates IL-6 expression, and the HOXA6 regulates cell differentiation and inflammation. The results of the quantitative trait locus (QTL) enrichment analysis showed that the DE lncRNAs were located in genomic regions previously associated with clinical mastitis, HDL cholesterol, bovine tuberculosis, paratuberculosis, and bovine leukosis susceptibility. The identified DE lncRNAs could allow the development of novel PTB diagnostic tools and have potential applications in breeding strategies for PTB-resistant cattle.https://www.frontiersin.org/articles/10.3389/fvets.2025.1601267/fulllong non-coding RNAsparatuberculosistranscriptomicsRNA-Seqbiomarkersgene regulation
spellingShingle Gerard Badia-Bringué
Victoria Asselstine
Ángela Cánovas
Marta Alonso-Hearn
Genome-wide long non-coding RNA expression profile and its regulatory role in the ileocecal valve from Mycobacterium avium subsp. paratuberculosis-infected cattle
Frontiers in Veterinary Science
long non-coding RNAs
paratuberculosis
transcriptomics
RNA-Seq
biomarkers
gene regulation
title Genome-wide long non-coding RNA expression profile and its regulatory role in the ileocecal valve from Mycobacterium avium subsp. paratuberculosis-infected cattle
title_full Genome-wide long non-coding RNA expression profile and its regulatory role in the ileocecal valve from Mycobacterium avium subsp. paratuberculosis-infected cattle
title_fullStr Genome-wide long non-coding RNA expression profile and its regulatory role in the ileocecal valve from Mycobacterium avium subsp. paratuberculosis-infected cattle
title_full_unstemmed Genome-wide long non-coding RNA expression profile and its regulatory role in the ileocecal valve from Mycobacterium avium subsp. paratuberculosis-infected cattle
title_short Genome-wide long non-coding RNA expression profile and its regulatory role in the ileocecal valve from Mycobacterium avium subsp. paratuberculosis-infected cattle
title_sort genome wide long non coding rna expression profile and its regulatory role in the ileocecal valve from mycobacterium avium subsp paratuberculosis infected cattle
topic long non-coding RNAs
paratuberculosis
transcriptomics
RNA-Seq
biomarkers
gene regulation
url https://www.frontiersin.org/articles/10.3389/fvets.2025.1601267/full
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