Nucleo-cytoplasmic RNA distribution responsible for maintaining neuroinflammatory microenvironment

RNA Biol. 2021 Nov 12;18(sup2):866-880. doi: 10.1080/15476286.2021.2004684. Epub 2021 Nov 29.

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; lncRNA; neuroinflammation; neuroinflammatory microenvironment; subcellular transcripts localization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism*
  • Cellular Microenvironment / genetics*
  • Computational Biology / methods
  • Cytoplasm / genetics
  • Cytoplasm / metabolism*
  • Disease Models, Animal
  • Disease Susceptibility
  • Gene Expression Profiling
  • Gene Ontology
  • Hemorrhage / complications
  • Mice
  • Microglia / metabolism
  • Neuroinflammatory Diseases / etiology*
  • Neuroinflammatory Diseases / metabolism
  • RNA Transport*
  • RNA, Long Noncoding / genetics

Substances

  • RNA, Long Noncoding

Grants and 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].