Long non-coding RNA normalisers in human brain tissue.

Area of Science:

• Molecular Biology
• Neuroscience
• Genomics

Background:

• Long non-coding RNAs (lncRNAs) play crucial roles in gene regulation, development, and neuronal plasticity.
• Accurate lncRNA expression profiling necessitates reliable normalization methods.
• No systematic analysis of lncRNA normalizers in human postmortem brain tissue existed.

Purpose of the Study:

• To identify stable long non-coding RNA (lncRNA) normalizers for human postmortem brain tissue.
• To evaluate lncRNA expression stability across different brain regions (cortex, white matter, cerebellum).
• To assess the impact of postmortem interval (PMI) on the stability of potential lncRNA normalizers.

Main Methods:

• Investigated expression stability of 90 lncRNAs in three human postmortem brain regions.
• Utilized bioinformatical analysis and the NormFinder algorithm for lncRNA classification.
• Analyzed the influence of postmortem intervals (PMI) on the expression of identified lncRNA normalizers.

Main Results:

• Identified 30, 22, and 41 suitable lncRNA normalizers in cortex, white matter, and cerebellum, respectively.
• Discovered 5 lncRNAs (LUST, IGF2AS, 7SK, HOXA6as, NDM29) with stable expression across all investigated brain regions.
• Confirmed that these 5 universal lncRNA normalizers exhibit stable expression within postmortem intervals (PMI) up to 27 hours.

Conclusions:

• The 5 identified universal lncRNAs are suitable references for accurate normalization in human brain lncRNA profiling.
• These normalizers facilitate reproducible lncRNA studies across multiple brain regions, even with extended postmortem intervals (PMI).
• The findings provide essential tools for advancing research in neurobiology and lncRNA function in the human brain.