Karyopherin Kap114p-mediated trans-repression controls ribosomal gene expression under saline stress

Chung Chi Liao, Sahana Shankar, Wen Chieh Pi, Chih Chia Chang, Golam Rizvee Ahmed, Wei Yi Chen, Kuo Chiang Hsia*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Nuclear accessibility of transcription factors controls gene expression, co-regulated by Ran-dependent nuclear localization and a competitive regulatory network. Here, we reveal that nuclear import factor-facilitated transcriptional repression attenuates ribosome biogenesis under chronic salt stress. Kap114p, one of the karyopherin-βs (Kap-βs) that mediates nuclear import of yeast TATA-binding protein (yTBP), exhibits a yTBP-binding affinity four orders of magnitude greater than its counterparts and suppresses binding of yTBP with DNA. Our crystal structure of Kap114p reveals an extensively negatively charged concave surface, accounting for high-affinity basic-protein binding. KAP114 knockout in yeast leads to a high-salt growth defect, with transcriptomic analyses revealing that Kap114p modulates expression of genes associated with ribosomal biogenesis by suppressing yTBP binding to target promoters, a trans-repression mechanism we attribute to reduced nuclear Ran levels under salinity stress. Our findings reveal that Ran integrates the nuclear transport pathway and transcription regulatory network, allowing yeast to respond to environmental stresses.

Original languageEnglish
Article numbere48324
JournalEMBO Reports
Volume21
Issue number7
DOIs
StatePublished - 3 Jul 2020

Keywords

  • high salinity
  • karyopherin-β
  • nucleocytoplasmic transport
  • TATA-box-binding protein
  • X-ray crystallography

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