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lncRNA - Long Non-coding RNAs02:39

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In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
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Functional identification of long non-coding RNAs induced by PM2.5 in microglia through microarray analysis.

Xue Liang1, Fanglin Di2, Haiyun Wei3

  • 1School of Public Health, Shandong First Medical University (Shandong Academy of Medical Sciences), Jinan, Shandong 250117, China; Medical Science and Technology Innovation Center, Shandong First Medical University (Shandong Academy of Medical Sciences), Jinan, Shandong 250117, China.

Ecotoxicology and Environmental Safety
|February 22, 2024
PubMed
Summary

Exposure to fine particulate matter (PM2.5) harms microglia, brain cells crucial for CNS health. This study identifies specific long non-coding RNAs (lncRNAs) involved in PM2.5 neurotoxicity, offering potential therapeutic targets.

Keywords:
Fine particulate matterLong non-coding RNAsMicrogliaNeurotoxicityTranscriptional factors

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Area of Science:

  • Environmental Health
  • Neuroscience
  • Molecular Biology

Background:

  • Atmospheric fine particulate matter (PM2.5) is a significant air pollutant with known adverse effects on the central nervous system (CNS).
  • The precise mechanisms underlying PM2.5-induced neurotoxicity remain largely unclear.
  • Long non-coding RNAs (lncRNAs) are implicated in various neurological diseases, suggesting their potential role in PM2.5 toxicity.

Purpose of the Study:

  • To investigate the neurotoxic effects of PM2.5 on microglia, a key immune cell in the CNS.
  • To identify differentially expressed lncRNAs (DElncRNAs) in response to PM2.5 exposure.
  • To elucidate the molecular mechanisms of PM2.5-induced neurotoxicity by analyzing DElncRNA-associated biological pathways and regulatory networks.

Main Methods:

  • Microglia (BV2 cell line) were exposed to varying concentrations of PM2.5 (5, 10, and 20 μg/cm²) for 24 hours.
  • Cell viability assays and structural damage assessments were performed to evaluate PM2.5 toxicity.
  • Microarray analysis was employed to identify DElncRNAs, followed by pathway enrichment analysis and identification of cis/trans-regulated mRNAs and transcriptional factors (TFs).

Main Results:

  • PM2.5 exposure decreased microglia viability, caused structural damage, and induced cell death.
  • Microarray analysis revealed significant changes in lncRNA expression profiles.
  • DElncRNAs were found to be enriched in pathways such as ferroptosis, IL-17 signaling, and NOD-like receptor signaling.
  • Key transcriptional factors (CEBPA, MYC, MEIS1, KLF4) regulating target mRNAs were identified in association with DElncRNAs.

Conclusions:

  • PM2.5 exerts detrimental effects on microglia, contributing to neurotoxicity.
  • This study provides a valuable resource of candidate lncRNAs and potential therapeutic targets for mitigating PM2.5-induced neurotoxicity.
  • Understanding the post-transcriptional regulation by lncRNAs is crucial for future research on PM2.5 neurotoxicity.