Comprehensive Analysis Of Aberrant Alternative Splicing And RNA Binding Proteins Associated With Age-Related Sensorineural Hearing Loss

Research has identified numerous altered gene processing events and their regulating proteins linked to age-related sensorineural hearing loss in a mouse model, with ISG15 emerging as a crucial regulator of these processes.

As we age, many of us experience a decline in hearing. Recent research sheds light on the intricate molecular changes contributing to age-related hearing loss, focusing on how our genes are “read” and expressed. Our genetic information, DNA, is first transcribed into messenger RNA (mRNA). Before this mRNA can be used to build proteins, it undergoes a crucial process called alternative splicing. Imagine a recipe with optional ingredients or steps; alternative splicing allows a single gene to produce multiple versions of a protein, each with slightly different functions, by selectively including or excluding certain segments of the mRNA.

This study investigated these alternative splicing events in the context of age-related hearing loss. It identified numerous specific changes in these gene processing steps, which were notably different in mice experiencing age-related hearing loss compared to healthy controls. Furthermore, the research pinpointed several “RNA binding proteins” (RBPs) that act like conductors, directing which segments of the mRNA are included or excluded during splicing.

The researchers found that certain RBPs were either more or less active in the aged, hearing-impaired mice. They also constructed networks illustrating how these altered RBPs influence the specific changes in gene splicing. A particularly significant finding was the identification of a protein called ISG15 as a key player in regulating alternative splicing events relevant to age-related hearing loss.

Understanding these complex molecular interactions—how RNA binding proteins orchestrate alternative splicing and how these processes go awry with age—provides valuable insights into the underlying causes of age-related sensorineural hearing loss. These findings open new avenues for developing potential therapeutic targets and disease markers, ultimately paving the way for better diagnosis and treatment strategies.