Sus1, Cdc31, and the Sac3 CID Region Form a Conserved Interaction Platform that Promotes Nuclear Pore Association and mRNA Export

Abstract

SummaryThe yeast Sac3:Cdc31:Sus1:Thp1 (TREX-2) complex facilitates the repositioning and association of actively transcribing genes with nuclear pores (NPCs)—“gene gating”—that is central to integrating transcription, processing, and mRNA nuclear export. We present here the crystal structure of Sus1 and Cdc31 bound to a central region of Sac3 (the CID domain) that is crucial for its function. Sac3CID forms a long, gently undulating α helix around which one Cdc31 and two Sus1 chains are wrapped. Sus1 has an articulated helical hairpin fold that facilitates its wrapping around Sac3. In vivo studies using engineered mutations that selectively disrupted binding of individual chains to Sac3 indicated that Sus1 and Cdc31 function synergistically to promote NPC association of TREX-2 and mRNA nuclear export. These data indicate Sac3CID provides a scaffold within TREX-2 to integrate interactions between protein complexes to facilitate the coupling of transcription and mRNA export during gene expression.

Structure of a trimeric nucleoporin complex reveals alternate oligomerization states

“…A related transport mechanism is responsible for the import of inner nuclear membrane proteins, which are synthesized into the endoplasmic reticulum and outer nuclear membrane (8). In addition to its central role in nucleocytoplasmic transport, the NPC is involved in various other important functions, such as chromatin organization, regulation of transcription, and DNA repair (9)(10)(11)(12).…”

Coupling pre-mRNA processing to transcription on the RNA factory assembly line

“…91,92 Sac3 interacts with Mex67/Mtr2 and a component of the nuclear pore complex, Nup1, and facilitates docking of mRNPs to the nuclear pore. 93,94 Moreover, the yeast SAGA complex, via its intrinsic component Sus1, localizes actively transcribing genes close to the nuclear pore and may also help mRNA export. Furthermore, the role of the SAGA complex and Thp1 in transcription elongation suggests that TREX-2, analogous to TREX, may define a pathway connecting transcription elongation with mRNA export.…”

Sem1

“…The N-terminal and middle domain (N + M) of Sac3 bind Thp1 and Mex67-Mtr2, while the C-terminal domain mediates its NPC targeting 8 and recruits the centrin Cdc31 as well as Sus1. 9,10 Recent works from several groups have demonstrated a requirement of TREX-2 in "gene gating," a process involving the dynamic repositioning of a…”