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Structure of transcription-export complex TREX revealed

TREX ("TRanscription-and-EXport complex") is a key player in the mRNA export pathway. In a new study published in eLife today, scientists from the lab of Clemens Plaschka report the three-dimensional structure of the human TREX core complex.

True to its name, messenger RNA (mRNA) conveys the instructions from our DNA genome to the cellular machinery that translates these into proteins. However, mRNA is produced in the cell’s nucleus, where the DNA is located, and must be transported into the cytoplasm before it can be translated. This poses a challenge: only a faithfully made mRNA, carrying all the necessary RNA modifications and partner proteins, should be allowed out of the nucleus. A key player in the mRNA export pathway is the transcription-and-export complex (TREX). In a new study published in eLife today, scientists from the lab of Clemens Plaschka report the three-dimensional structure of the human TREX core complex.

Ticking off the protein to-do list

Newly made mRNA undergoes several RNA modifications such as capping, splicing, and cleavage and polyadenylation. Like checkmarks on a to-do list, proteins bind the mRNA after each modification step to mark its successful completion. The TREX complex then binds the modified mRNA-protein assembly to license it for export into the cytoplasm. “However, little is currently known about the mechanisms and structural basis of how mRNA packaging and export licensing occur”, explains Plaschka. “TREX binds several of these checkpoint marks on the mature mRNA and prepares it for export, yet how can a single complex select the mature mRNA and license it efficiently?”

To shed light on this process, Plaschka and his group, including Master student Thomas Pühringer and Postdoc Ulrich Hohmann, who is jointly affiliated with the lab of Julius Brennecke (Institute of Molecular Biotechnology, also at the Vienna BioCenter), used cryo-electron microscopy to determine the three-dimensional structure of the TREX complex at 3.3 Ångström resolution – with a surprise. “We had assumed that the human TREX core would be a complex of seven different proteins, each in a single copy. To our astonishment, we instead found that TREX forms a large multimer: it assembles into a 28-subunit tetramer, with each protein present in four copies.” 

Multiplicity increases efficiency

This unexpected organisation can explain how TREX can simultaneously bind several “checkmarks” on the maturing mRNA. “The tetrameric TREX complex contains multiple binding sites for maturation marks. Once one of the TREX monomers has bound one mark, the remaining three monomers would be brought into close proximity of the mRNA, making the recognition of subsequent marks more likely. Similarly, this can also explain how the subsequent licensing of mRNA for export is made more efficient, by providing multiple binding sites for loading the so-called mRNA export factor onto mRNA.”