期刊
FRONTIERS IN MOLECULAR NEUROSCIENCE
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fnmol.2019.00326
关键词
tRNA-derived small RNA; spinal cord injury; sequencing; bioinformatics; BDNF
资金
- National Key R&D Program of China [2018YFF0301104]
- National Natural Science Foundation of China [81870979]
- Special Fund for Basic Scientific Research of Central Public Research Institutes [2018CZ1, 2019CZ-1]
- Basic Scientific Research Foundation of China Rehabilitation Research Center [2018ZX-30]
- Beijing Municipal Science and Technology Commission [Z181100004118004, Z171100001017076]
- Beijing Science and Technology Major Project [D161100002816004]
- Capital Health Research and Development of Special [2018-1-6011]
Spinal cord injury (SCI) is mostly caused by trauma. As the primary mechanical injury is unavoidable, a focus on the underlying molecular mechanisms of the SCI-induced secondary injury is necessary to develop promising treatments for patients with SCI. Transfer RNA-derived small RNA (tsRNA) is a novel class of short, non-coding RNA, possessing potential regulatory functions in various diseases. However, the functional roles of tsRNAs in traumatic SCI have not been determined yet. We used a combination of sequencing, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), bioinformatics, and luciferase reporter assay to screen the expression profiles and identify the functional roles of tsRNAs after SCI. As a result, 297 differentially expressed tsRNAs were identified in rats' spinal cord 1 day after contusion. Of those, 155 tsRNAs were significantly differentially expressed: 91 were significantly up-regulated, whereas 64 were significantly down-regulated after SCI (fold change > 1.5; P < 0.05). Bioinformatics analyses revealed candidate tsRNAs (tiRNA-Gly-GCC-001, tRF-Gly-GCC-012, tRF-Gly-GCC-013, and tRF-Gly-GCC-016) that might play regulatory roles through the mitogen-activated protein kinase (MAPK) and neurotrophin signaling pathways by targeting brain-derived neurotrophic factor (BDNF). We validated the candidate tsRNAs and found opposite trends in the expression levels of the tsRNAs and BDNF after SCI. Finally, tiRNA-Gly-GCC-001 was identified to target BDNF using the luciferase reporter assay. In summary, we found an altered tsRNA expression pattern and predicted tiRNA-Gly-GCC-001 might be involved in the MAPK and neurotrophin pathways by targeting the BDNF, thus regulating the post-SCI pathophysiologic processes. This study provides novel insights for future investigations to explore the mechanisms and therapeutic targets for SCI.
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