Nucleo-cytoplasmic RNA distribution responsible for maintaining neuroinflammatory microenvironment

ABSTRACT

Subcellular localization of transcripts is highly associated with regulation of gene expression, synthesis of protein, and also the development of the human brain cortex. Although many mechanisms are prevalent in the occurrence of neuroinflammation, the mechanisms based on differences in subcellular localization of transcripts have not been explored. To characterize the dynamic profile of nuclear and cytoplasmic transcripts during the progress of haemorrhage-induced neuroinflammation, we isolated nucleo-cytoplasmic RNA fractions of oxyhaemoglobin (oxy-Hb) treated microglia cells and sequenced both fractions. We discovered that cytoplasmic retained genes were the major forces to maintain the neuroinflammatory microenvironment with 10 hub genes and 40 conserved genes were identified. Moreover, antisense RNA Gm44096 and lincRNA Gm47270, which co-expressed with a crowd of inflammatory genes in the cytoplasm, were discovered as regulatory strategies for sustaining the neuroinflammatory microenvironment. Thus, our study provides a new perspective on understanding haemorrhage-induced neuroinflammation and also reveals a mechanism of lncRNA responsible for maintaining the neuroinflammatory microenvironment.

KEYWORDS:

• Microglia
• neuroinflammatory microenvironment
• neuroinflammation
• lncRNA
• subcellular transcripts localization

Acknowledgments

This work was supported by the Young Elite Scientist Sponsorship Program by the China Association for Science and Technology, the National Natural Science Foundation of China (81771278, 81801176, 81971132), the Sichuan Science and Technology Program (2019JDTD0004, 2021031), the Luzhou Science and Technology Program (2020-RCM-68, 2019LZXNYDZ06), and the Southwest Medical University Program (2020ZRQNB072, 2020ZRQNB022).

Data availability

The sequence data generated in this study have been submitted to the NCBI GEO database under accession number GSE160934. Supplementary information is supplied as a separate file.

Authors contribution

Y.L. and C.K. conducted all the RNA-seq libraries construction, RT-qPCR assays, FISH, Western blot, cell viability assay, NO measurement assay and cell culture work; Y.L., C.K. and K.X. performed the extraction of nuclear and cytoplasmic RNA; Z.B. performed all bioinformatics analysis; Y.H. and L.G. helped to performed the statistics and some data visualization; Y.L., C.K., Q.T. and X.Q. conducted lncRNA knockdown and overexpression assays; L.Z. supervised experiments regarding plasmid construction and analysis of the data. G.D. helped for co-expression analysis and manuscript proofreading; J.P. supervised the experiment regarding extraction of nuclear and cytoplasmic RNA; Y.J. and S.Y. conceived the project. C.K., J.P., Y.J. and S.Y. designed the study, analysed the data, and wrote the manuscript with input from all authors. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Supplementary Material

Supplemental data for this article can be accessed here

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [81771278]; the National Natural Science Foundation of China [81801176]; the National Natural Science Foundation of China [81971132]; the Young Elite Scientist Sponsorship Program ; the southwest medical university program [2020ZRQNB022]; the People’s Government of Luzhou-Southwest Medical University Science and Technology Strategic Cooperation Project [the People’s Government of Luzhou-Southwest Medical University Science and Technology Strategic Cooperation Project 2019LZXNYDZ06]; the Luzhou Science and Technology Program [2020-RCM-68]; the sichuan science and technology program [2021031]; the southwest medical university program [2020ZRQNB072]; the Sichuan Science and Technology Program [2019JDTD0004].