PMID- 26839368
OWN - NLM
STAT- MEDLINE
DCOM- 20170524
LR  - 20191210
IS  - 1533-3450 (Electronic)
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 27
IP  - 9
DP  - 2016 Sep
TI  - Far Upstream Element-Binding Protein 1 Binds the 3' Untranslated Region of PKD2 
      and Suppresses Its Translation.
PG  - 2645-57
LID - 10.1681/ASN.2015070836 [doi]
AB  - Autosomal dominant polycystic kidney disease pathogenesis can be recapitulated in 
      animal models by gene mutations in or dosage alterations of polycystic kidney 
      disease 1 (PKD1) or PKD2, demonstrating that too much and too little PKD1/PKD2 
      are both pathogenic. Gene dosage manipulation has become an appealing approach by 
      which to compensate for loss or gain of gene function, but the mechanisms 
      controlling PKD2 expression remain incompletely characterized. In this study, 
      using cultured mammalian cells and dual-luciferase assays, we found that the 3' 
      untranslated region (3'UTR) of PKD2 mRNA inhibits luciferase protein expression. 
      We then identified nucleotides 691-1044, which we called 3FI, as the 3'UTR 
      fragment necessary for repressing the expression of luciferase or PKD2 in this 
      system. Using a pull-down assay and mass spectrometry we identified far upstream 
      element-binding protein 1 (FUBP1) as a 3FI-binding protein. In vitro 
      overexpression of FUBP1 inhibited the expression of PKD2 protein but not mRNA. In 
      embryonic zebrafish, FUBP1 knockdown (KD) by morpholino injection increased PKD2 
      expression and alleviated fish tail curling caused by morpholino-mediated KD of 
      PKD2. Conversely, FUBP1 overexpression by mRNA injection significantly increased 
      pronephric cyst occurrence and tail curling in zebrafish embryos. Furthermore, 
      FUBP1 binds directly to eukaryotic translation initiation factor 4E-binding 
      protein 1, indicating a link to the translation initiation complex. These results 
      show that FUBP1 binds 3FI in the PKD2 3'UTR to inhibit PKD2 translation, 
      regulating zebrafish disease phenotypes associated with PKD2 KD.
CI  - Copyright (c) 2016 by the American Society of Nephrology.
FAU - Zheng, Wang
AU  - Zheng W
AD  - Membrane Protein Disease and Cancer Research Centre, Provincial Innovation 
      Center, Hubei University of Technology, Wuhan, China; Membrane Protein Disease 
      Research Group, Department of Physiology.
FAU - Shen, Fan
AU  - Shen F
AD  - Membrane Protein Disease Research Group, Department of Physiology, Medical 
      Research Center, Zhongnan Hospital, Wuhan University, Wuhan, China; and.
FAU - Hu, Ruikun
AU  - Hu R
AD  - School of Life Sciences and Technology, Tongji University, Shanghai, China.
FAU - Roy, Birbickram
AU  - Roy B
AD  - Department of Biological Sciences, and.
FAU - Yang, JungWoo
AU  - Yang J
AD  - Membrane Protein Disease Research Group, Department of Physiology.
FAU - Wang, Qian
AU  - Wang Q
AD  - Membrane Protein Disease Research Group, Department of Physiology.
FAU - Zhang, Fan
AU  - Zhang F
AD  - School of Life Sciences and Technology, Tongji University, Shanghai, China.
FAU - King, Jennifer C
AU  - King JC
AD  - Membrane Protein Disease Research Group, Department of Physiology.
FAU - Sergi, Consolato
AU  - Sergi C
AD  - Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, 
      Alberta, Canada;
FAU - Liu, Song-Mei
AU  - Liu SM
AD  - Medical Research Center, Zhongnan Hospital, Wuhan University, Wuhan, China; and.
FAU - Cordat, Emmanuelle
AU  - Cordat E
AD  - Membrane Protein Disease Research Group, Department of Physiology.
FAU - Tang, Jingfeng
AU  - Tang J
AD  - Membrane Protein Disease and Cancer Research Centre, Provincial Innovation 
      Center, Hubei University of Technology, Wuhan, China;
FAU - Cao, Ying
AU  - Cao Y
AD  - School of Life Sciences and Technology, Tongji University, Shanghai, China.
FAU - Ali, Declan
AU  - Ali D
AD  - Department of Biological Sciences, and.
FAU - Chen, Xing-Zhen
AU  - Chen XZ
AD  - Membrane Protein Disease and Cancer Research Centre, Provincial Innovation 
      Center, Hubei University of Technology, Wuhan, China; Membrane Protein Disease 
      Research Group, Department of Physiology, xzchen@ualberta.ca.
LA  - eng
GR  - Canadian Institutes of Health Research/International
PT  - Journal Article
DEP - 20160202
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
RN  - 0 (3' Untranslated Regions)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (FUBP1 protein, human)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (TRPP Cation Channels)
RN  - 0 (polycystic kidney disease 2 protein)
RN  - EC 3.6.4.- (DNA Helicases)
SB  - IM
MH  - 3' Untranslated Regions/*physiology
MH  - Animals
MH  - Cells, Cultured
MH  - DNA Helicases/*metabolism
MH  - DNA-Binding Proteins/*metabolism
MH  - *Protein Biosynthesis
MH  - RNA-Binding Proteins
MH  - TRPP Cation Channels/*genetics
MH  - Zebrafish
PMC - PMC5004656
OTO - NOTNLM
OT  - 3'UTR
OT  - ADPKD
OT  - RNA-binding protein
OT  - translational regulation
OT  - zebrafish
EDAT- 2016/02/04 06:00
MHDA- 2017/05/26 06:00
PMCR- 2017/09/01
CRDT- 2016/02/04 06:00
PHST- 2015/07/29 00:00 [received]
PHST- 2015/11/24 00:00 [accepted]
PHST- 2016/02/04 06:00 [entrez]
PHST- 2016/02/04 06:00 [pubmed]
PHST- 2017/05/26 06:00 [medline]
PHST- 2017/09/01 00:00 [pmc-release]
AID - ASN.2015070836 [pii]
AID - 2015070836 [pii]
AID - 10.1681/ASN.2015070836 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 2016 Sep;27(9):2645-57. doi: 10.1681/ASN.2015070836. Epub 2016 
      Feb 2.