Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a 3' poly-A tail, forming the mature mRNA. Only those mature mRNAs that associate with RNA-binding proteins (RBPs) forming ribonucleoprotein particles are prevented from degradation and are selectively transported out of the nucleus for protein synthesis. mRNAs that do not associate with RBPs are not transported out of the nucleus and hence not translated into proteins. Alternatively, if a mature mRNA binds a complementary microRNA, it undergoes degradation, thereby inhibiting protein synthesis.

However, once the mRNA is translated, the newly synthesized protein undergoes modification that affects its activity. For example, adding functional groups, such as methyl groups, phosphate, or acetyl groups, may activate or inactivate the protein. In contrast, adding multiple ubiquitin proteins to a substrate protein marks them for degradation. Thus, ubiquitination regulates protein stability and its functional activity.