Deciphering the Role of Alternative Splicing in Molecular Assemblies: Are Immortalized Cell Lines Good Data Sources?

Bao, Yue

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Deciphering the Role of Alternative Splicing in Molecular Assemblies: Are Immortalized Cell Lines Good Data Sources?

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Alternative splicing is critical in diversifying the structure and function of gene products. In this work, we explored the impact of alternative splicing on the structure and function of key molecular complexes, or “large macromolecular assemblies (LMMA)”, which carry out numerous essential functions in human cells. We proposed the Alternative Splicing Impact Factor (ASIF), an innovative framework that quantifies variations of proteins associated with a molecular assembly driven by alternative splicing. The framework was first applied to characterize two LMMAs, ribosome and RNA polymerases. We found a substantial amount of protein variations driven by alternative splicing in different tissues/cells, suggesting that the impact of alternative splicing was highly tissue specific. Results highlighted significant discrepancies of alternative splicing impact on these highly conservative molecular assemblies between healthy tissues and immortalized cell lines, and within immortalized cell lines, which suggested that even though immortalized cell lines are widely used in various research fields, they should be processed with caution.

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