Abstract
SummaryThe TREX-2 complex integrates mRNA nuclear export into the gene expression pathway and is based on a Sac3 scaffold to which Thp1, Sem1, Sus1, and Cdc31 bind. TREX-2 also binds the mRNA nuclear export factor, Mex67:Mtr2, through the Sac3 N-terminal region (Sac3N). Here, we characterize Chaetomium thermophilum TREX-2, show that the in vitro reconstituted complex has an annular structure, and define the structural basis for interactions between Sac3, Sus1, Cdc31, and Mex67:Mtr2. Crystal structures show that the binding of C. thermophilum Sac3N to the Mex67 NTF2-like domain (Mex67NTF2L) is mediated primarily through phenylalanine residues present in a series of repeating sequence motifs that resemble those seen in many nucleoporins, and Mlp1 also binds Mex67:Mtr2 using a similar motif. Deletion of Sac3N generated growth and mRNA export defects in Saccharomyces cerevisiae, and we propose TREX-2 and Mlp1 function to facilitate export by concentrating mature messenger ribonucleoparticles at the nuclear pore entrance.
Highlights
The export of mRNA from the nucleus to the cytoplasm is a crucial step in the gene expression pathway in eukaryotes, enabling the genetic message encoded in the genome to be used for protein synthesis by ribosomes
Crystal structures show that the binding of C. thermophilum Sac3 N-terminal region (Sac3N) to the Mex67 NTF2-like domain (Mex67NTF2L) is mediated primarily through phenylalanine residues present in a series of repeating sequence motifs that resemble those seen in many nucleoporins, and Mlp1 binds Mex67:Mtr2 using a similar motif
Deletion of Sac3N generated growth and mRNA export defects in Saccharomyces cerevisiae, and we propose Transcription export complex 2 (TREX-2) and Mlp1 function to facilitate export by concentrating mature messenger ribonucleoparticles at the nuclear pore entrance
Summary
The export of mRNA from the nucleus to the cytoplasm is a crucial step in the gene expression pathway in eukaryotes, enabling the genetic message encoded in the genome to be used for protein synthesis by ribosomes. RNPs exit the nucleus through nuclear pore complexes (NPCs), 8-fold symmetric, supramolecular assemblies embedded in the nuclear envelope that are composed of proteins called nucleoporins. Some FG nucleoporins are distributed symmetrically across the NPC, others are distributed asymmetrically and are found at either the nuclear or cytoplasmic face (Terry and Wente, 2007). Transport through NPCs is facilitated by transport factors that bind a macromolecular cargo in one compartment and release it in the other, and which can overcome the barrier function through interactions with the nucleoporin FG sequence motifs. In addition to contributing to chromatin maintenance and transcription, nuclear basket components facilitate mRNA export by docking mRNPs to the NPC through an interaction with the mRNA binding protein Nab (Green et al, 2003; Grant et al, 2008)
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