Transcription and Splicing Dynamics in Single Cells

Division Of Basic Sciences - Nci

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Abstract

The over-arching aim of recent years is to understand the basis of fidelity in transcription and splicing and how to exploit errors in fidelity in disease. For example, we have made significant progress in understanding how transcription factors and enhancers control gene regulation and maintain accurate transfer of genetic information. We find that transcription factors such as glucocorticoid receptor rely on a mechanism called 'kinetic proofreading.' Similarly, this kinetic proofreading mechanism is used in splicing fidelity. Importantly, when cells make errors, especially in splicing, the resulting mRNA are translated into cryptic peptides which are presented on the surface of cells as neo-antigens which are recognized by the immune system. Thus, we speculate these splicing errors can be exploited for immunotherapy.