Escorting mRNAs – the multifunctional and divergent roles of cap-chaperones in post-transcriptional gene expression

Transcripts undergo a variety of processing steps - including splicing, nuclear export and translation - to ultimately produce their protein product in the required form. Deviations in these steps can produce proteins with altered or ablated function. Central to mRNA processing is the methyl-7-guanosine (m7G) 'cap' on the 5' end of transcripts. This cap engages cap-binding proteins, termed cap-chaperones, which escort transcripts on their path towards protein production. There are two main cap-chaperones: the cap-binding complex (CBC), which was traditionally thought to act only in the nucleus, and the eukaryotic translation initiation factor eIF4E, thought to act in only the cytoplasm. However, studies have shown that both cap-chaperones localize to nuclear and cytoplasmic compartments, complicating the traditional understanding of their housekeeping roles in mRNA processing. In this updated context, this Review provides an overview of cap-chaperone function, describing their roles both in the nucleus and cytoplasm. We discuss mechanisms by which cap-chaperones differentially engage specific mRNA processing machineries and target transcripts, leading to altered mRNA fate. Finally, we briefly review dysregulation of cap-chaperones and the subsequent disruption of mRNA processing observed in cancer. In all, cap-chaperone choice is likely a significant determinant in mRNA fate.