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Cell Stress and Chaperones

, Volume 23, Issue 4, pp 571–579 | Cite as

Heat shock factor 4 regulates the expression of HSP25 and alpha B-crystallin by associating with DEXD/H-box RNA helicase UAP56

  • Xiukun Cui
  • Wenxiu Han
  • Jing Li
  • Riping Feng
  • Zheng Zhou
  • JiuLi Han
  • Mengyuan Li
  • Shuangfeng Wang
  • Wanting Zhang
  • Qin Lei
  • Jun Zhang
  • Yutiao Liu
  • Yanzhong Hu
Original Paper

Abstract

Heat shock factor 4 controls the transcription of small heat shock proteins (e.g., HSP25, alpha B-cyrstallin, and r-crystallin), that play important roles in modulating lens proteostasis. However, the molecular mechanism underlying HSF4-mediated transcription is still unclear. Using yeast two hybrid, we found that HSF4 interacts with the ATP-dependent DEXD/H-box RNA helicase UAP56, and their interaction in lens epithelial cell line was further confirmed by GST-pull down assay. UAP56 is a vital regulator of pre-mRNA splicing and mature mRNA nuclear export. The immunofluorescence assay showed that HSF4 and UBA56 co-localize with each other in the nucleus of lens epithelial cells. Ectopic UAP56 upregulated HSF4-controlled HSP25 and alpha B-crystallin proteins expression, while knocking down UAP56 by shRNA reversed it. Moreover, UAP56 interacts with and facilitates the nuclear exportation of HSP25 and alpha B-crystallin mRNA without impacting their total mRNA expression level. In lens tissues, both UAP56 and HSF4 are expressed in the same nucleus of lens fiber cells, and their expression levels are simultaneously reduced with fiber cell maturation. Taken together, these data suggested that UAP56 is a novel regulator of HSF4 and might upregulate HSF4’s downstream mRNA maturation and nuclear exportation.

Keywords

HSF4 UAP56 HSP25 Alpha B-crystallin Posttranscriptional modification 

Notes

Funding information

This work is supported by NSFC grant foundations of U1604171, 81270985, 81570825, and 81400387, and Henan Education committee talent program for the innovative technology 14IRTSTHN019 and 16A310005

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Copyright information

© Cell Stress Society International 2017

Authors and Affiliations

  • Xiukun Cui
    • 1
  • Wenxiu Han
    • 1
  • Jing Li
    • 1
  • Riping Feng
    • 1
  • Zheng Zhou
    • 1
  • JiuLi Han
    • 1
  • Mengyuan Li
    • 1
  • Shuangfeng Wang
    • 1
  • Wanting Zhang
    • 2
  • Qin Lei
    • 2
  • Jun Zhang
    • 1
  • Yutiao Liu
    • 3
  • Yanzhong Hu
    • 1
    • 2
  1. 1.National Joint Laboratory For Antibody Drug Enginerring, Henan-international Union Laboratory of Antibody Medicine, Department of Cell Biology and Genetics, School of Basic Medical ScienceHenan UniversityKaifengChina
  2. 2.Kaifeng Key Laboratory of Cataract and Myopia, Institute of Eye diseaseKaifeng Central HospitalKaifengChina
  3. 3.Department of Cell biology and AnatomyAugusta UniversityAugustaUSA

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