Comprehensive transcriptome analysis reveals altered mRNA splicing and post-transcriptional changes in the aged mouse...

Area of Science:

• Neuroscience
• Molecular Biology
• Genomics

Background:

• Understanding molecular changes in the aging brain is vital for addressing cognitive decline and neurodegenerative diseases.
• Previous studies on mRNA alterations in brain aging are limited by cohort health and age variability.

Purpose of the Study:

• To investigate mRNA splicing and dynamics in the aging mouse brain.
• To identify age-related molecular changes impacting brain function and transcriptome.
• To explore the role of RNA-binding proteins in age-related transcriptomic reshaping.

Main Methods:

• Utilized a combination of short- and long-read sequencing technologies.
• Performed extensive bioinformatic analyses on aging mouse brain samples.
• Controlled for cohort health and age factors in the study design.

Main Results:

• Identified age-related differences in messenger RNA (mRNA) isoform usage.
• Observed decreased mRNA dynamics and an increase in neuronal gene expression modules.
• Found a reduced abundance of mRNA isoforms targeted by nonsense-mediated RNA decay.

Conclusions:

• mRNA splicing events are significantly altered during brain aging.
• RNA-binding protein regulation may be a key factor in reshaping the aged brain transcriptome.
• These findings underscore the importance of studying mRNA splicing in the context of brain aging and neurodegeneration.