Polyadenylation and nuclear export of mRNAs.

Murray Stewart

The Journal of biological chemistry 2019 Mar 01

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In eukaryotes, the separation of translation from transcription by the nuclear envelope enables mRNA modifications such as capping, splicing, and polyadenylation. These modifications are mediated by a spectrum of ribonuclear proteins that associate with preRNA transcripts, coordinating the different steps and coupling them to nuclear export, ensuring that only mature transcripts reach the cytoplasmic translation machinery. Although the components of this machinery have been identified and considerable functional insight has been achieved, a number of questions remain outstanding about mRNA nuclear export and how it is integrated into the nuclear phase of the gene expression pathway. Nuclear export factors mediate mRNA transit through nuclear pores to the cytoplasm, after which these factors are removed from the mRNA, preventing transcripts from returning to the nucleus. However, as outlined in this review, several aspects of the mechanism by which transport factor binding and release are mediated remain unclear, as are the roles of accessory nuclear components in these processes. Moreover, the mechanisms by which completion of mRNA splicing and polyadenylation are recognized, together with how they are coordinated with nuclear export, also remain only partially characterized. One attractive hypothesis is that dissociating poly(A) polymerase from the cleavage and polyadenylation machinery could signal completion of mRNA maturation and thereby provide a mechanism for initiating nuclear export. The impressive array of genetic, molecular, cellular, and structural data that has been generated about these systems now provides many of the tools needed to define the precise mechanisms involved in these processes and how they are integrated. © 2019 Stewart.