Transcriptional homeostasis: a mechanism of protein quality control

Sickle cell anaemia confirms that minor mutations in protein sequence can have catastrophic effects. However, RNA transcription depends on polymerases that have low fidelity and introduce errors at a rate of 10(-5) substitutions/base synthesised. For many large proteins translation of these errors could result in significant loss of function, while for others (for example, cell surface signalling proteins) variability of protein expression could be advantageous. This paper outlines a mechanism that enables proteins to modulate error incorporation (variability) into RNAs sysnthesised by RNA polymerase--transcriptional homeostasis--thereby modulating, and error correcting, their own sysnthesis. Transcriptional homeostasis is a fundamental regulatory mechanism relevant to control of gene expression.