SUMMARY PARAGRAPH for THP1
Thp1p is an RNA-binding protein which forms the stable TREX-2 (TRanscription EXport) complex with Sac3p, Sus1p, and Cdc31p (3, 4, 8). TREX-2 is associated with the nuclear pore, is essential for nuclear mRNA export, and plays a role in mRNP biogenesis and genome maintenance (9, 8, 10, 11, 12, 13). TREX-2 functions by docking the mRNP to specific nucleoporins at the nuclear entrance of the nuclear pore complex (NPC) (3). TREX-2 components Sus1p and Cdc31p function synergistically to promote association of TREX-2 with the NPC, where it is anchored via the nucleoporin Nup1p (14, 13). The TREX-2 complex facilitates the repositioning and association of actively transcribing genes with nuclear pores -"gene gating"- that is central to integrating transcription, processing, and mRNA nuclear export (14).
TREX and TREX-2, the two main mRNA export complexes, are also required for efficient transcription-coupled repair (TCR) in yeast (15). Thp1p (TREX-2) and two other proteins previously shown to control transcription-associated recombination, Hpr1p and Tho2p (members of the THO complex), act in the same "pathway" connecting transcription elongation with the incidence of mitotic recombination (1). TREX-2, together with THO/TREX, defines a specific pathway connecting transcription elongation with export via an RNA-dependent dynamic process that provides a feedback mechanism for the control of transcription and the preservation of genetic integrity of transcribed DNA regions (11).
Sgf73p, a subunit of the SAGA histone acetyltransferase complex, mediates recruitment of Thp1p and Sac3p to SAGA and their stable interaction with Sus1p-Cdc31p to form TREX-2 and target it to the nuclear pore complex (16). Targeting of Thp1p to the nuclear pore complex is perturbed in cells mutant for SEM1, a component of the lid subcomplex of the regulatory subunit of the 26S proteasome (17).
Mutants disrupted for THP1 grow slowly, are cold-sensitive and sporulate with reduced efficiency (18). Deletion of THP1 also strongly stimulates recombination and impairs transcription (1, 4). sac3Delta confers a transcription defect and hyper-recombination phenotype identical to that of thp1Delta (4), and mutations in either Sac3p or Thp1p affect genome integrity and lead to strong mRNA export defects (3, 4, 19, 11). The poly(A)+ RNA-binding heterogeneous nuclear ribonucleoprotein Nab2p is a multicopy suppressor of the transcription and RNA export defects of thp1Delta cells (4). thp1Delta cells also exhibit diploid-specific sensitivity to doxorubicin (20).
Orthologs of Thp1p, the TREX-2 complex as a whole, and Nup1p, have been identified in Arabidopsis (13). Homologs of Thp1p have also been identified in Schizosaccharomyces pombe, Caenorhabditis elegans, Drosophila melanogaster, and Homo sapiens (1).
Last updated: 2010-06-07