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

• Published in: EMBO reports Vol. 21; no. 7; pp. e48324 - n/a
• Main Authors: Liao, Chung‐Chi, Shankar, Sahana, Pi, Wen‐Chieh, Chang, Chih‐Chia, Ahmed, Golam Rizvee, Chen, Wei‐Yi, Hsia, Kuo‐Chiang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03-07-2020; Blackwell Publishing Ltd; John Wiley and Sons Inc
• Subjects: Abiotic stress; Affinity; beta Karyopherins - genetics; Biosynthesis; Cell Nucleus - genetics; Cell Nucleus - metabolism; Crystal structure; Deoxyribonucleic acid; DNA; DNA structure; EMBO09; EMBO20; Environmental stress; Gene Expression; Gene silencing; Genes; high salinity; Imports; Karyopherins; karyopherin‐β; Localization; Nuclear Proteins - metabolism; Nuclear transport; nucleocytoplasmic transport; Proteins; Ribosomes - genetics; Ribosomes - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Salinity; Salinity effects; Salts; Stresses; TATA‐box‐binding protein; Transcription factors; X‐ray crystallography; Yeast; Yeasts; high salinity; karyopherin‐β; nucleocytoplasmic transport; TATA‐box‐binding protein; X‐ray crystallography; X-ray crystallography; TATA-box-binding protein; karyopherin-β
• ISSN: 1469-221X; 1469-3178
• DOI: 10.15252/embr.201948324

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.
Synopsis
This study reveals that the karyopherin Kap114p facilitates transcriptional repression and attenuates ribosome biogenesis under chronic salt stress.
Crystal structure of Kap114p reveals that it structurally resembles Cse1p.
Kap114p displays a very high affinity towards yTBP and suppresses binding of yTBP to DNA.
Kap114p modulates the expression of genes associated with ribosomal biogenesis
via
trans‐repression of yTBP‐mediated transcription under salinity stress.
Ran integrates the nuclear transport pathway and transcription regulatory network, allowing yeast to respond to environmental stresses.
Graphical Abstract
This study reveals that the karyopherin Kap114p facilitates transcriptional repression and attenuates ribosome biogenesis under chronic salt stress.