Thioredoxin interacting protein (Txnip) forms redox sensitive high molecular weight nucleoprotein complexes
Cristiane Lumi Hirata1, Shinji Ito2, Hiroshi Masutani1
1Tenri Health Care University, Tenri, 80-1 Bessho-cho, Tenri, Nara, 632-0018, Japan; Department of Infection and Prevention, Institute for Frontier and Medical Sciences, Kyoto University, 53, Kawahara-cho, Shogoin, Sakyo, Kyoto, 606-8507, Japan.
Archives of Biochemistry and Biophysics
|November 1, 2019
Summary
Thioredoxin interacting protein (Txnip) forms large, redox-sensitive protein complexes with RNA. These high-molecular-weight complexes suggest a novel mechanism for Txnip in regulating cellular processes.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Thioredoxin interacting protein (Txnip) is an α-arrestin protein involved in cancer suppression and energy metabolism.
- Understanding Txnip's molecular mechanisms requires identifying its binding partners and complex formation.
Purpose of the Study:
- To identify protein binding partners of Txnip.
- To investigate the formation and composition of Txnip-containing complexes.
Main Methods:
- Tandem affinity purification and proteomics to identify binding partners.
- Native PAGE and DTT treatment to analyze complex formation and redox sensitivity.
- RNAse treatment and RNA-seq to assess RNA involvement.
Main Results:
- Identified HSP90, HSP70, and Prp31 as Txnip binding partners.
- Demonstrated Txnip forms high molecular weight (1000-1300 kDa) nuclear complexes.
- Showed these complexes are redox-sensitive and involve RNA, with differential RNA expression observed.
Conclusions:
- Txnip forms transient, higher-order nucleoprotein complexes.
- These complexes involve multiple binding partners and RNAs.
- This complex formation provides a model for Txnip's regulatory functions in signaling pathways.
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