Tissue-Specific Proteins and Functional Implications

Tissue-specific gene expression can result in the presence or absence of certain protein interactions and complexes, leading to profound functional differences of biological processes between the tissues. In this study, we integrate human gene expression data based on RNA-sequencing with protein interactions, domains and complexes to analyze the functional implications of their tissue specificity. This reveals that tissue specificity is characterized by much fewer proteins, domains, interactions, and complexes than previously thought. In contrast to previous microarray studies, our analysis based on RNA-sequencing suggests that tissue-specific protein interactions are less common and mainly involved with transmembrane transport and receptor activation. Additionally, tissue-specific protein domains show enrichments in DNA-related functions. This confirms that receptor-activated signaling processes and transcriptional regulation are two key factors for tissue specificity. Furthermore, many protein complexes are widely expressed regardless of their size, and their formation is frequently controlled by very few tissue-specific proteins. Interestingly, the number of alternative transcripts is increased for widely expressed genes. This suggests that alternative splicing plays a prominent role in generating specific functional characteristics of tissues.