Dual role of the ddx5/ddx17 RNA helicases in the control of the pro-migratory NFAT5 transcription factor
Authors: E Dardenne
S Jauliac
M Fougère
D Auboeuf
S Germann
B Gaudineau
S Samaan
E Zonta
M Dutertre
L Gratadou
Journal: Oncogene (2012)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Ddx5; Ddx17; RNA helicases; Transcription; Splicing
Affiliations: Université de Lyon, Lyon, France.

Abstract:  Ddx5 and ddx17 are two highly related RNA helicases involved in both transcription and splicing. These proteins coactivate transcription factors involved in cancer such as the estrogen receptor alpha, p53 and beta-catenin. Ddx5 and ddx17 are part of the splicing machinery and can modulate alternative splicing, the main mechanism increasing the proteome diversity. Alternative splicing also has a role in gene expression level regulation when it is coupled to the nonsense-mediated mRNA decay (NMD) pathway. In this work, we report that ddx5 and ddx17 have a dual role in the control of the pro-migratory NFAT5 transcription factor. First, ddx5 and ddx17 act as transcriptional coactivators of NFAT5 and are required for activating NFAT5 target genes involved in tumor cell migration. Second, at the splicing level, ddx5 and ddx17 increase the inclusion of NFAT5 exon 5. As exon 5 contains a pre-mature translation termination codon, its inclusion leads to the regulation of NFAT5 mRNAs by the NMD pathway and to a decrease in NFAT5 protein level. Therefore, we demonstrated for the first time that a transcriptional coregulator can simultaneously regulate the transcriptional activity and alternative splicing of a transcription factor. This dual regulation, where ddx5 and ddx17 enhance the transcriptional activity of NFAT5 although reducing its protein expression level, suggests a critical role for ddx5 and ddx17 in tumor cell migration through the fine regulation of NFAT5 pathway. 

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PubPeer comments:
  Since the discovery of coordination polymers (CPs), these materials have been intensively studied due to their potential applications in areas such as luminescence, gas adsorption, and cytotoxic agents (7 u201310). - [7]. Feng Y, Fan H, Zhong Z, Wang H, Qiu D. Cd3(MoO4)(TeO3)2: a polar 3D compound containing d10u2013d0 SCALP-effect cations. Inorg Chem 2016; 55: 11987u201311992, doi: 10.1021 acs.inorgchem.6b02117. - [8] Feng Y, Li M, Fan H, Huang Q, Qiu D, Shi H. A novel open-framework copper borophosphate containing 1-D borophosphate anion with 10-MR windows and 12-MR channels. Dalton Trans 2015; 44: 894u2013897, doi:10.1039 C4DT02840F. - [9] Duan CW, Hu LX, Ma JL. Ionic liquids as an efficient medium for the mechanochemical synthesis of u03b1-AlH3 nano-composites. J Mater Chem A 2018; 6: 6309u20136318, doi: 10.1039 C8TA00533H. - [10] Duan CW, Cao YZ, Hu LX, Fu D, Ma JL. Synergistic effect of TiF3 on the dehydriding property of a-AlH3 nano-composite. Mater Lett 2019; 238: 254u2013257, doi: 10.1016 j.matlet.2018.12.028. Are these papers really about metal-organic coordination polymers? Could the author check? , 
 This is one of a large number of coordination-chemistry papers that appear to have all been written according to a template. - Most draw on two papers by Y. Feng et al. and one by C.-W. Duan et al to illustrate the broad range of applications and properties of MOFs. Notably, these are not papers about MOFs. - - Y. Feng, H. Fan, Z. Zhong, H. Wang, D. Qiu, Inorg. Chem. 2016, 55, 11987u201311992.  Cd3(MoO4)(TeO3)2: A Polar 3D Compound Containing d10-d0 SCALP-Effect Cations - - Y. Feng, M. Li, H. Fan, Q. Huang, D. Qiu, H. Shi, Dalton Trans. 2015, 44, 894u2013897.  A Novel Open-Framework Copper Borophosphate Containing 1-D Borophosphate Anion with 10-MR Windows and 12-MR Channels - - C. W. Duan, L. X. Hu, J. L. Ma, J. Mater. Chem. A 2018, 6, 6309u20136318  Ionic liquids as an efficient medium for the mechanochemical synthesis of u03b1-AlH3 nano-composites - The cluster is sometimes accompanied by less relevant references and clusters of references. Frequently co-occuring papers include - - Duan CW, Cao YZ, Hu LX, Fu D, Ma JL (2019)  Synergistic effect of TiF3 on the dehydriding property of a-AlH3 nano-composite . - - K. Wang, J. Pang, L. Li, S. Zhou, Y. Li, T. Zhang, Front. Chem. Sci. Eng. 2018, 12, 376u2013382.  Synthesis of hydrophobic carbon nanotubes reduced graphene oxide composite films by flash light irradiation - - K. Wu, K. Du, G. Hu, J. Mater. Chem. A 2018, 6, 1057u20131066  Red-blood-cell-like (NH4) [Fe2(OH)(PO4)2]u00b72H2O particles: Fabrication and application in high-performance LiFePO4 cathode materials - - Yin K, Chu DK, Dong XR, Wang C, Duan JA, He J (2017)  Femtosecond laser induced robust periodic nanoripples structured mesh for highly efficient oil-water separation . Nanoscale 9:14229u201314235. - - Davila-Manzanilla SG, Figueroa-de-Paz Y, Mejia C, Ruiz-Azuara L (2017)  Synergistic effects between a copper-based metal Casiopeu00edna III-Ia and cisplatin . Eur J Med Chem 129:266u2013274 - The vast majority of email identities for corresponding authors were formed by taking an underscore-separated name and appending **666** or 66 . I am advised that these are auspicious numbers with positive associations. So one possibility is that the authors all decided independently to generate email accounts with this format. The alternative is that *some outside contractor* handled the task of negotiating with journals (generating these disposable accounts in the process) - perhaps also the task of writing the manuscripts, using a single Bibliography file to save time. The complete list [is here] . ,