Interplay between transcription and RNA-binding proteins in the regulation of Gene expression

Abstract

The control of gene expression is a complex and extensively regulated process that involves numerous nuclear and cytoplasmic steps. Pre-mRNAs are produced by RNA Polymerase II (RNAPII) and co-transcriptionally processed, by capping, splicing and polyadenylation machineries. The mature mRNA is exported to cytoplasm where it undergoes translation and eventually degradation. At all phases of their life cycle, mRNAs associate with a distinct set of RNA-binding proteins (RBPs) to form ribonucleoprotein (RNP) complexes (mRNPs). The “mRNP code” determines the fate of the associated mRNAs and thus is a major denominator of cellular gene expression networks. I will discuss different aspects of RNA processing, including alternative splicing and translation, focusing on how these individual steps are interconnected. I will first present the role of a nucleo-cytoplasmic shutting splicing factor, the SR protein family member, SRSF1, in mRNA translation. I will then illustrate how the modulation of core transcription machinery (RNAPII elongation rate) can lead to different splicing outcomes. I will demonstrate that careful coordination of the different processes in mRNA life cycle ensures homeostasis and is essential during development.