Comparative transcriptome profiling reveals RNA splicing alterations and biological function in patients exposed to...

Area of Science:

• Genetics
• Molecular Biology
• Audiology

Background:

• Genetic factors significantly influence susceptibility to noise-induced hearing loss (NIHL).
• Alternative splicing (AS), a post-transcriptional gene expression mechanism, is implicated in disease pathogenesis but understudied in NIHL.
• Investigating AS in NIHL can uncover novel insights into disease mechanisms.

Purpose of the Study:

• To comprehensively analyze RNA splicing alterations in NIHL.
• To identify differentially expressed genes and alternative splicing events associated with NIHL.
• To explore the functional pathways involved in NIHL pathogenesis through AS.

Main Methods:

• RNA sequencing (RNA-seq) was performed on blood samples from NIHL patients and normal-hearing controls with similar noise exposure.
• Differential gene expression and alternative splicing analyses were conducted.
• Functional enrichment analysis was applied to identify significantly affected pathways.

Main Results:

• 356 differentially expressed genes, including 23 transcription factors, were identified between NIHL patients and controls.
• 56 aberrant alternative splicing events involving 41 differentially expressed genes were detected.
• Exon skipping was the most prevalent type of differentially alternative splicing (DAS) event (54%).
• DAS genes and differentially expressed genes were significantly enriched in autophagy and mitochondria-related pathways.

Conclusions:

• Alternative splicing events are implicated in the susceptibility and pathogenesis of NIHL.
• Autophagy and mitochondrial pathways are significantly associated with AS alterations in NIHL.
• These findings highlight the importance of AS in understanding NIHL and suggest potential therapeutic targets.