Molecular Mechanism of m6A Methylation Modification Genes <i>METTL3</i> and <i>FTO</i> in Regulating Heat Stress in Sheep
Heat stress is an important environmental factor affecting livestock production worldwide. Primary hepatocytes and preadipocytes derived from Hu sheep were used to establish a heat stress model. Quantitative reverse transcriptase-PCR (qRT-PCR) analysis showed that heat induction significantly increa...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-07-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/15/11926 |
| _version_ | 1797586726137364480 |
|---|---|
| author | Bowen Chen Chao Yuan Tingting Guo Jianbin Liu Bohui Yang Zengkui Lu |
| author_facet | Bowen Chen Chao Yuan Tingting Guo Jianbin Liu Bohui Yang Zengkui Lu |
| author_sort | Bowen Chen |
| collection | DOAJ |
| description | Heat stress is an important environmental factor affecting livestock production worldwide. Primary hepatocytes and preadipocytes derived from Hu sheep were used to establish a heat stress model. Quantitative reverse transcriptase-PCR (qRT-PCR) analysis showed that heat induction significantly increased the expression levels of heat stress protein (HSP) genes and the N<sup>6</sup>-methyladenosine (m6A) methylation modification genes: methyltransferase-like protein 3 (<i>METTL3</i>), methyltransferase-like protein 14 (<i>METTL14</i>), and fat mass and obesity associated protein (<i>FTO</i>). Heat stress simultaneously promoted cell apoptosis. Transcriptome sequencing identified 3980 upregulated genes and 2420 downregulated genes related to heat stress. A pathway enrichment analysis of these genes revealed significant enrichment in fatty acid biosynthesis, degradation, and the PI3K-Akt and peroxisome proliferator-activated receptor (PPAR) signaling pathways. Overexpression of <i>METTL3</i> in primary hepatocytes led to significant downregulation of <i>HSP60</i>, <i>HSP70</i>, and <i>HSP110</i>, and significantly increased mRNA m6A methylation; <i>FTO</i> interference generated the opposite results. Primary adipocytes showed similar results. Transcriptome analysis of cells under <i>METTL3</i> (or <i>FTO</i>) inference and overexpression revealed differentially expressed genes enriched in the mitogen-activated protein kinase (MAPK) signaling pathways, as well as the PI3K-Akt and Ras signaling pathways. We speculate that <i>METTL3</i> may increase the level of m6A methylation to inhibit fat deposition and/or inhibit the expression of HSP genes to enhance the body’s resistance to heat stress, while the <i>FTO</i> gene generated the opposite molecular mechanism. This study provides a scientific basis and theoretical support for sheep feeding and management practices during heat stress. |
| first_indexed | 2024-03-11T00:26:13Z |
| format | Article |
| id | doaj.art-429bf1ae259441a68c6ca8739852026d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T00:26:13Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-429bf1ae259441a68c6ca8739852026d2023-11-18T22:58:01ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-07-0124151192610.3390/ijms241511926Molecular Mechanism of m6A Methylation Modification Genes <i>METTL3</i> and <i>FTO</i> in Regulating Heat Stress in SheepBowen Chen0Chao Yuan1Tingting Guo2Jianbin Liu3Bohui Yang4Zengkui Lu5Key Laboratory of Animal Genetics and Breeding on the Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, ChinaKey Laboratory of Animal Genetics and Breeding on the Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, ChinaKey Laboratory of Animal Genetics and Breeding on the Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, ChinaKey Laboratory of Animal Genetics and Breeding on the Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, ChinaKey Laboratory of Animal Genetics and Breeding on the Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, ChinaKey Laboratory of Animal Genetics and Breeding on the Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, ChinaHeat stress is an important environmental factor affecting livestock production worldwide. Primary hepatocytes and preadipocytes derived from Hu sheep were used to establish a heat stress model. Quantitative reverse transcriptase-PCR (qRT-PCR) analysis showed that heat induction significantly increased the expression levels of heat stress protein (HSP) genes and the N<sup>6</sup>-methyladenosine (m6A) methylation modification genes: methyltransferase-like protein 3 (<i>METTL3</i>), methyltransferase-like protein 14 (<i>METTL14</i>), and fat mass and obesity associated protein (<i>FTO</i>). Heat stress simultaneously promoted cell apoptosis. Transcriptome sequencing identified 3980 upregulated genes and 2420 downregulated genes related to heat stress. A pathway enrichment analysis of these genes revealed significant enrichment in fatty acid biosynthesis, degradation, and the PI3K-Akt and peroxisome proliferator-activated receptor (PPAR) signaling pathways. Overexpression of <i>METTL3</i> in primary hepatocytes led to significant downregulation of <i>HSP60</i>, <i>HSP70</i>, and <i>HSP110</i>, and significantly increased mRNA m6A methylation; <i>FTO</i> interference generated the opposite results. Primary adipocytes showed similar results. Transcriptome analysis of cells under <i>METTL3</i> (or <i>FTO</i>) inference and overexpression revealed differentially expressed genes enriched in the mitogen-activated protein kinase (MAPK) signaling pathways, as well as the PI3K-Akt and Ras signaling pathways. We speculate that <i>METTL3</i> may increase the level of m6A methylation to inhibit fat deposition and/or inhibit the expression of HSP genes to enhance the body’s resistance to heat stress, while the <i>FTO</i> gene generated the opposite molecular mechanism. This study provides a scientific basis and theoretical support for sheep feeding and management practices during heat stress.https://www.mdpi.com/1422-0067/24/15/11926heat stressm6A methylation<i>METTL3</i><i>FTO</i>sheep |
| spellingShingle | Bowen Chen Chao Yuan Tingting Guo Jianbin Liu Bohui Yang Zengkui Lu Molecular Mechanism of m6A Methylation Modification Genes <i>METTL3</i> and <i>FTO</i> in Regulating Heat Stress in Sheep International Journal of Molecular Sciences heat stress m6A methylation <i>METTL3</i> <i>FTO</i> sheep |
| title | Molecular Mechanism of m6A Methylation Modification Genes <i>METTL3</i> and <i>FTO</i> in Regulating Heat Stress in Sheep |
| title_full | Molecular Mechanism of m6A Methylation Modification Genes <i>METTL3</i> and <i>FTO</i> in Regulating Heat Stress in Sheep |
| title_fullStr | Molecular Mechanism of m6A Methylation Modification Genes <i>METTL3</i> and <i>FTO</i> in Regulating Heat Stress in Sheep |
| title_full_unstemmed | Molecular Mechanism of m6A Methylation Modification Genes <i>METTL3</i> and <i>FTO</i> in Regulating Heat Stress in Sheep |
| title_short | Molecular Mechanism of m6A Methylation Modification Genes <i>METTL3</i> and <i>FTO</i> in Regulating Heat Stress in Sheep |
| title_sort | molecular mechanism of m6a methylation modification genes i mettl3 i and i fto i in regulating heat stress in sheep |
| topic | heat stress m6A methylation <i>METTL3</i> <i>FTO</i> sheep |
| url | https://www.mdpi.com/1422-0067/24/15/11926 |
| work_keys_str_mv | AT bowenchen molecularmechanismofm6amethylationmodificationgenesimettl3iandiftoiinregulatingheatstressinsheep AT chaoyuan molecularmechanismofm6amethylationmodificationgenesimettl3iandiftoiinregulatingheatstressinsheep AT tingtingguo molecularmechanismofm6amethylationmodificationgenesimettl3iandiftoiinregulatingheatstressinsheep AT jianbinliu molecularmechanismofm6amethylationmodificationgenesimettl3iandiftoiinregulatingheatstressinsheep AT bohuiyang molecularmechanismofm6amethylationmodificationgenesimettl3iandiftoiinregulatingheatstressinsheep AT zengkuilu molecularmechanismofm6amethylationmodificationgenesimettl3iandiftoiinregulatingheatstressinsheep |