Negative feedback regulation by HuR controls TRIM21 expression and function in response to UV radiation.

Scientific Reports
Abhishek GuhaPartho Sarothi Ray

Abstract

The E3 ubiquitin ligase TRIM21 plays a crucial role as a negative regulator of innate immune responses. Recent evidence has also indicated the involvement of TRIM21 in the genotoxic stress response and suppressing tumorigenesis. Our previous work has demonstrated a new function of TRIM21 in inhibiting p53 protein synthesis by degrading the RNA-binding protein HuR in response to UV radiation. This suggested a pro-oncogenic role of TRIM21. In this study, we have shown that TRIM21 enhances the proliferation of MCF7 breast carcinoma cells and counteracts the decrease in cell proliferation and colony formation caused by UV-induced DNA damage. Further, this pro-oncogenic role of TRIM21 in response to DNA damage is mediated by its degradation of HuR. Conversely, we found that HuR binds to a U-rich element in the 3'UTR of TRIM21 mRNA and activates its translation, thereby constituting a negative feedback loop. We found that dihydrotanshinone-I (DHTS-I), a plant-derived product which prevents HuR binding to specific RNAs, prevented HuR-mediated upregulation of TRIM21, while increasing the HuR-mediated upregulation of p53. Together, these findings demonstrate a negative feedback regulation between TRIM21 and HuR, which may play an import...Continue Reading

References

Mar 21, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tomonori IshiiChikao Morimoto
May 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Alexander EspinosaMarie Wahren-Herlenius
Apr 3, 2007·Proceedings of the National Academy of Sciences of the United States of America·Leo C JamesJohn Trowsdale
Oct 31, 2007·Molecular and Cellular Biology·Stefanie GalbánMyriam Gorospe
Mar 26, 2008·Biochemical and Biophysical Research Communications·Tadanori YamochiChikao Morimoto
Apr 19, 2008·Proceedings of the National Academy of Sciences of the United States of America·Anthony H KeebleLeo C James
Jun 6, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ryusuke YoshimiKeiko Ozato
Jul 29, 2009·The Journal of Experimental Medicine·Alexander EspinosaMarie Wahren-Herlenius
Nov 3, 2010·Nucleic Acids Research·Kate B CookTimothy R Hughes
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
Jul 5, 2011·Molecular Cell·Svetlana LebedevaNikolaus Rajewsky
Aug 6, 2011·Molecular Cell·Subramanya Srikantan, Myriam Gorospe
Sep 22, 2011·Wiley Interdisciplinary Reviews. RNA·Kotb Abdelmohsen, Myriam Gorospe
Nov 4, 2011·Molecular Cancer Research : MCR·Lisa E YoungDan A Dixon
Dec 20, 2011·Biochemical and Biophysical Research Communications·Siti Nur Aisyah JauharohSeiji Kawano
Dec 29, 2011·Frontiers in Bioscience (Landmark Edition)·Subramanya Srikantan, Myriam Gorospe
Jun 16, 2012·International Journal of Rheumatology·Ryusuke YoshimiKeiko Ozato
Jun 20, 2012·Current Protein & Peptide Science·Subramanya SrikantanMyriam Gorospe
Aug 4, 2012·RNA Biology·Prasanna BhatSaumitra Das
May 15, 2013·International Journal of Molecular Sciences·Jun WangBaocheng Wang
Jul 11, 2013·Proceedings of the National Academy of Sciences of the United States of America·Marina VaysburdLeo C James
Aug 27, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Maria SjöstrandMarie Wahren-Herlenius
May 16, 2014·Nucleic Acids Research·Inbal PazYael Mandel-Gutfreund
Jan 18, 2015·Progress in Molecular Biology and Translational Science·William A McEwan, Leo C James
Jun 10, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Qianshan DingHonggang Yu
Sep 9, 2015·The Journal of Cell Biology·Tomonori KimuraVojo Deretic
Nov 11, 2016·Cancer Biology & Therapy·Jeffrey Q Nguyen, Rosalyn B Irby
Jan 5, 2017·Proceedings of the National Academy of Sciences of the United States of America·William A McEwanLeo C James
Jan 28, 2017·Scientific Reports·Michiru NishitaYasuhiro Minami
Aug 19, 2017·Science·Mathias UhlenFredrik Ponten
Sep 22, 2017·Nucleic Acids Research·Preet LalAlessandro Provenzani
Dec 7, 2018·International Journal of Biological Macromolecules·Yue JinYouzhong Wan
Jan 23, 2019·Current Biology : CB·Milica Vunjak, Gijs A Versteeg
Jun 12, 2019·American Journal of Respiratory Cell and Molecular Biology·Lian LiJing Zhao

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Methods Mentioned

BETA
transfection
PAR-CLIP
immunoprecipitation
electrophoresis
PCR

Software Mentioned

CLIP
mFold
PAR

Related Concepts

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