Epitranscriptomic m6A regulation following spinal cord injury

doi:10.1002/jnr.24763

. 2021 Mar;99(3):843-857.

doi: 10.1002/jnr.24763. Epub 2020 Dec 3.

Epitranscriptomic m6A regulation following spinal cord injury

Lingyan Xing¹, Yunyun Cai², Tuo Yang³, Weiwei Yu¹, Mengdie Gao¹, Rui Chai¹, Sujun Ding⁴, Jinhuan Wei⁵, Jingying Pan⁶, Gang Chen^{6

7}

Affiliations

¹ Key Laboratory of Neuroregeneration of Jiangsu and the Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
² Department of Physiology, School of medicine, Nantong University, Nantong, China.
³ Department of Hand Surgery, China-Japan Union Hospital of Jilin University, Changchun, China.
⁴ Department of Medical Ultrasound, Affiliated Hospital of Nantong University, Nantong, China.
⁵ Basic Medical Research Center, School of Medicine, Nantong University, Nantong, China.
⁶ Department of Tissue and Embryology, Medical School of Nantong University, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
⁷ Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, China.

PMID: 33271625
DOI: 10.1002/jnr.24763

Epitranscriptomic m6A regulation following spinal cord injury

Lingyan Xing et al. J Neurosci Res. 2021 Mar.

. 2021 Mar;99(3):843-857.

doi: 10.1002/jnr.24763. Epub 2020 Dec 3.

Authors

Lingyan Xing¹, Yunyun Cai², Tuo Yang³, Weiwei Yu¹, Mengdie Gao¹, Rui Chai¹, Sujun Ding⁴, Jinhuan Wei⁵, Jingying Pan⁶, Gang Chen^{6

7}

Affiliations

¹ Key Laboratory of Neuroregeneration of Jiangsu and the Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
² Department of Physiology, School of medicine, Nantong University, Nantong, China.
³ Department of Hand Surgery, China-Japan Union Hospital of Jilin University, Changchun, China.
⁴ Department of Medical Ultrasound, Affiliated Hospital of Nantong University, Nantong, China.
⁵ Basic Medical Research Center, School of Medicine, Nantong University, Nantong, China.
⁶ Department of Tissue and Embryology, Medical School of Nantong University, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
⁷ Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, China.

PMID: 33271625
DOI: 10.1002/jnr.24763

Abstract

RNA methylation is involved in multiple physiological and pathological processes. However, the role of RNA methylation in spinal cord regeneration has not been reported. In this study, we find an altered m6A (N6-methyladenosine) RNA methylation profiling following zebrafish spinal cord injury (SCI), in line with an altered transcription level of the m6A methylase Mettl3. Interestingly, many of the differential m6A-tagged genes associated with neural regeneration are hypomethylated, but their transcription levels are upregulated in SCI. Moreover, we find that METTL3 may be important for spinal cord regeneration. We also show a conserved feature of METTL3 changes in mouse SCI model, in which the expression of METTL3 is increased in both astrocytes and neural stem cells. Together, our results indicate that m6A RNA methylation is dynamic and conserved following SCI and may contribute to spinal cord regeneration.

Keywords: Mettl3 (Methyltransferase Like 3); RNA methylation; RRID:AB_11212597; RRID:AB_2338072; RRID:AB_2338840; RRID:AB_2721254; RRID:AB_305313; m6A (N6-methyladenosine); spinal cord injury.

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References

REFERENCES

1. Ai, X., Ye, Z., Yao, Y., Xiao, J., You, C., Xu, J., Huang, X. I., Zhong, J., Fan, M., Song, X., Shi, H., Zhang, D., & Zhao, C. (2020). Endothelial autophagy: An effective target for radiation-induced cerebral capillary damage. Scientific Reports, 10(1), 1-13. https://doi.org/10.1038/s41598-019-57234-9
1. Anderson, M. A., Burda, J. E., Ren, Y., Ao, Y., O'Shea, T. M., Kawaguchi, R., Coppola, G., Khakh, B. S., Deming, T. J., & Sofroniew, M. V. (2016). Astrocyte scar formation aids central nervous system axon regeneration. Nature, 532(7598), 195-200. https://doi.org/10.1038/nature17623
1. Anderson, M. A., O'Shea, T. M., Burda, J. E., Ao, Y., Barlatey, S. L., Bernstein, A. M., Kim, J. H., James, N. D., Rogers, A., Kato, B., Wollenberg, A. L., Kawaguchi, R., Coppola, G., Wang, C., Deming, T. J., He, Z., Courtine, G., & Sofroniew, M. V. (2018). Required growth facilitators propel axon regeneration across complete spinal cord injury. Nature, 561(7723), 396-400. https://doi.org/10.1038/s41586-018-0467-6
1. Barbieri, I., Tzelepis, K., Pandolfini, L., Shi, J., Millán-Zambrano, G., Robson, S. C., Aspris, D., Migliori, V., Bannister, A.J., Han, N., De Braekeleer, E., Ponstingl, H., Hendrick, A., Vakoc, C.R., Vassiliou, G. S., & Kouzarides, T. (2017). Promoter-bound METTL3 maintains myeloid leukaemia by m6A-dependent translation control. Nature, 552(7683), 126-131. https://doi.org/10.1038/nature24678.
1. Bernardos, R. L., Barthel, L. K., Meyers, J. R., & Raymond, P. A. (2007). Late-stage neuronal progenitors in the retina are radial Müller glia that function as retinal stem cells. Journal of Neuroscience, 27(26), 7028-7040. https://doi.org/10.1523/JNEUROSCI.1624-07.2007

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[1] Ai, X., Ye, Z., Yao, Y., Xiao, J., You, C., Xu, J., Huang, X. I., Zhong, J., Fan, M., Song, X., Shi, H., Zhang, D., & Zhao, C. (2020). Endothelial autophagy: An effective target for radiation-induced cerebral capillary damage. Scientific Reports, 10(1), 1-13. https://doi.org/10.1038/s41598-019-57234-9

[2] Ai, X., Ye, Z., Yao, Y., Xiao, J., You, C., Xu, J., Huang, X. I., Zhong, J., Fan, M., Song, X., Shi, H., Zhang, D., & Zhao, C. (2020). Endothelial autophagy: An effective target for radiation-induced cerebral capillary damage. Scientific Reports, 10(1), 1-13. https://doi.org/10.1038/s41598-019-57234-9

[3] Anderson, M. A., Burda, J. E., Ren, Y., Ao, Y., O'Shea, T. M., Kawaguchi, R., Coppola, G., Khakh, B. S., Deming, T. J., & Sofroniew, M. V. (2016). Astrocyte scar formation aids central nervous system axon regeneration. Nature, 532(7598), 195-200. https://doi.org/10.1038/nature17623

[4] Anderson, M. A., Burda, J. E., Ren, Y., Ao, Y., O'Shea, T. M., Kawaguchi, R., Coppola, G., Khakh, B. S., Deming, T. J., & Sofroniew, M. V. (2016). Astrocyte scar formation aids central nervous system axon regeneration. Nature, 532(7598), 195-200. https://doi.org/10.1038/nature17623

[5] Anderson, M. A., O'Shea, T. M., Burda, J. E., Ao, Y., Barlatey, S. L., Bernstein, A. M., Kim, J. H., James, N. D., Rogers, A., Kato, B., Wollenberg, A. L., Kawaguchi, R., Coppola, G., Wang, C., Deming, T. J., He, Z., Courtine, G., & Sofroniew, M. V. (2018). Required growth facilitators propel axon regeneration across complete spinal cord injury. Nature, 561(7723), 396-400. https://doi.org/10.1038/s41586-018-0467-6

[6] Anderson, M. A., O'Shea, T. M., Burda, J. E., Ao, Y., Barlatey, S. L., Bernstein, A. M., Kim, J. H., James, N. D., Rogers, A., Kato, B., Wollenberg, A. L., Kawaguchi, R., Coppola, G., Wang, C., Deming, T. J., He, Z., Courtine, G., & Sofroniew, M. V. (2018). Required growth facilitators propel axon regeneration across complete spinal cord injury. Nature, 561(7723), 396-400. https://doi.org/10.1038/s41586-018-0467-6

[7] Barbieri, I., Tzelepis, K., Pandolfini, L., Shi, J., Millán-Zambrano, G., Robson, S. C., Aspris, D., Migliori, V., Bannister, A.J., Han, N., De Braekeleer, E., Ponstingl, H., Hendrick, A., Vakoc, C.R., Vassiliou, G. S., & Kouzarides, T. (2017). Promoter-bound METTL3 maintains myeloid leukaemia by m6A-dependent translation control. Nature, 552(7683), 126-131. https://doi.org/10.1038/nature24678.

[8] Barbieri, I., Tzelepis, K., Pandolfini, L., Shi, J., Millán-Zambrano, G., Robson, S. C., Aspris, D., Migliori, V., Bannister, A.J., Han, N., De Braekeleer, E., Ponstingl, H., Hendrick, A., Vakoc, C.R., Vassiliou, G. S., & Kouzarides, T. (2017). Promoter-bound METTL3 maintains myeloid leukaemia by m6A-dependent translation control. Nature, 552(7683), 126-131. https://doi.org/10.1038/nature24678.

[9] Bernardos, R. L., Barthel, L. K., Meyers, J. R., & Raymond, P. A. (2007). Late-stage neuronal progenitors in the retina are radial Müller glia that function as retinal stem cells. Journal of Neuroscience, 27(26), 7028-7040. https://doi.org/10.1523/JNEUROSCI.1624-07.2007

[10] Bernardos, R. L., Barthel, L. K., Meyers, J. R., & Raymond, P. A. (2007). Late-stage neuronal progenitors in the retina are radial Müller glia that function as retinal stem cells. Journal of Neuroscience, 27(26), 7028-7040. https://doi.org/10.1523/JNEUROSCI.1624-07.2007

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Epitranscriptomic m6A regulation following spinal cord injury

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Epitranscriptomic m6A regulation following spinal cord injury

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