Splicing accuracy varies across human introns, tissues and age

Area of Science:

• Molecular Biology
• Genetics
• Bioinformatics

Background:

• Alternative splicing, a key process in gene expression, impacts most human genes.
• Errors in alternative splicing (mis-splicing) are implicated in aging and various diseases.

Approach:

• Analyzed RNA sequencing data from ~14,000 control samples across 42 human body sites.
• Focused on split reads mapping to known transcripts to identify mis-splicing events.
• Utilized public data on short-hairpin RNA knockdowns of spliceosomal components.

Key Points:

• Mis-splicing rates vary across introns and tissues, influenced by spliceosome component abundance.
• RNA-binding proteins play a significant role in regulating mis-splicing.
• Age is positively correlated with increased mis-splicing.
• Mis-splicing affects genes associated with neurodegenerative diseases.

Conclusions:

• Characterizing mis-splicing provides insights into its role in human disease.
• Findings are crucial for interpreting long-read RNA sequencing data accurately.
• Understanding splicing inaccuracies can advance disease research and therapeutic strategies.