Structural basis of mRNA maturation: Time to put it together.

In eukaryotes, the expression of genetic information begins in the cell nucleus with precursor messenger RNA (pre-mRNA) transcription and processing into mature mRNA. The mRNA is subsequently recognized and packaged by proteins into an mRNA ribonucleoprotein complex (mRNP) and exported to the cytoplasm for translation. Each of the nuclear mRNA maturation steps is carried out by a dedicated molecular machine. Here, we highlight recent structural and mechanistic insights into how these machines function, including the capping enzyme, the spliceosome, the 3'-end processing machinery, and the transcription-export complex. While we increasingly understand individual steps of nuclear gene expression, many questions remain. For example, we are only beginning to reveal how mature mRNAs are recognized and packaged for nuclear export and how mRNA maturation events are coupled to transcription and to each other. Advances in the preparation of recombinant and endogenous protein-nucleic acid complexes, cryo-electron microscopy, and machine learning promise exciting insights into the mechanisms of nuclear gene expression and its spatial organization.