TY - JOUR T1 - Karyopherin Kap114p regulates TATA-binding protein-mediated transcription JF - bioRxiv DO - 10.1101/411223 SP - 411223 AU - Chung-Chi Liao AU - Sahana Shankar AU - Golam Rizvee Ahmed AU - Kuo-Chiang Hsia Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/09/07/411223.abstract N2 - Gene expression is regulated by nuclear accessibility of transcription factors controlled by transport receptors and competitive inhibitors. Multiple karyopherin-βs (Kap-βs) facilitate nuclear import of yeast TATA-binding protein (yTBP). However, only Kap114p suppresses temperature-sensitive yTBP mutations, suggesting Kap114p executes undefined non-transport functions. We show that yTBP preferably binds Kap114p with an affinity three orders of magnitude higher than other Kap-βs facilitating yTBP nuclear import. Our crystal structure of Kap114p reveals an extensively negatively-charged concave surface, accounting for high-affinity basic-protein binding. Furthermore, we biochemically demonstrate that two intra-HEAT-repeat inserts act as regulatory TBP-binding domains carried by TBP-associated factor 1 (TAF1-TAND), suppressing binding of yTBP with DNA and the transcription factor IIA. Remarkably, dual-knockout of Kap114 and TAF1-TAND in yeast synergistically suppresses cell growth. Our study reveals that Kap114p has a dual function that modulates the nuclear localization and activity of yTBP, illuminating how the nuclear transport machinery regulates yTBP-mediated transcription. ER -