Human DBR1 modulates the recycling of snRNPs to affect alternative RNA splicing and contributes to the suppression of cancer development

Oncogene
B HanP Fei

Abstract

The contribution of RNA processing to tumorigenesis is understudied. Here, we report that the human RNA debranching enzyme (hDBR1), when inappropriately regulated, induces oncogenesis by causing RNA processing defects, for example, splicing defects. We found that wild-type p53 and hypoxia-inducible factor 1 co-regulate hDBR1 expression, and insufficient hDBR1 leads to a higher rate of exon skipping. Transcriptomic sequencing confirmed the effect of hDBR1 on RNA splicing, and metabolite profiling supported the observation that neoplasm is triggered by a decrease in hDBR1 expression both in vitro and in vivo. Most importantly, when modulating the expression of hDBR1, which was found to be generally low in malignant human tissues, higher expression of hDBR1 only affected exon-skipping activity in malignant cells. Together, our findings demonstrate previously unrecognized regulation and functions of hDBR1, with immediate clinical implications regarding the regulation of hDBR1 as an effective strategy for combating human cancer.

References

Nov 6, 1987·Science·P A Sharp, D Eisenberg
Jul 12, 1985·Science·B Ruskin, M R Green
Feb 1, 1996·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·A R KornblihttA F Muro
Sep 13, 2003·Science·Shih-Peng ChanSoo-Chen Cheng
Dec 21, 2004·Cancer Cell·Peiwen FeiWafik S El-Deiry
Apr 20, 2005·Oncogene·Sandra L Harris, Arnold J Levine
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Melanie D OhiThomas Walz
Feb 21, 2008·Nucleic Acids Research·Kaiping GaoKinji Ohno
Dec 24, 2008·Nucleic Acids Research·Rei YoshimotoMutsuhito Ohno
Feb 26, 2009·Cell·Markus C WahlReinhard Lührmann
Apr 8, 2009·Molecular and Cellular Biology·Naoyuki KataokaMutsuhito Ohno
Nov 18, 2009·The Journal of Pathology·Amanda J Ward, Thomas A Cooper
Jan 30, 2010·Nature·Timothy W Nilsen, Brenton R Graveley
Aug 14, 2010·Cell·Michael J MoorePamela A Silver
Nov 13, 2010·Nucleic Acids Research·Alexander W PastuszakAlan D Frankel
Jan 25, 2013·RNA·Janine O IlaganMelissa S Jurica
Apr 16, 2013·International Journal of Molecular Sciences·Yunping QiuWei Jia
Aug 24, 2013·Oncotarget·Jayabal PanneerselvamPeiwen Fei
Dec 18, 2013·Bioinformatics·Andreas KrämerStuart Tugendreich
Jan 24, 2014·Nature Reviews. Molecular Cell Biology·A Gregory Matera, Zefeng Wang
Feb 15, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yunping QiuWei Jia
Jun 21, 2014·Molecular Cell·Russ P Carstens
Mar 19, 2015·Annual Review of Biochemistry·Yeon Lee, Donald C Rio
May 21, 2015·IUBMB Life·Oliver Bischof, Ricardo Iván Martínez-Zamudio
Jun 6, 2015·Cell·Markus C Wahl, Reinhard Lührmann
Apr 14, 2016·Cancer Cell·Adam M Schmitt, Howard Y Chang
Jun 18, 2016·Science·Bruce A Sullenger, Smita Nair
Jun 22, 2016·Cancer Research·Alexander A SvoronosFrank J Slack
Nov 3, 2016·Development·Michaela Frye, Sandra Blanco
Dec 9, 2016·Proceedings of the National Academy of Sciences of the United States of America·Nathaniel E ClarkP John Hart

❮ Previous
Next ❯

Citations

Aug 8, 2018·Proceedings of the National Academy of Sciences of the United States of America·Gaëlle J S Talhouarne, Joseph G Gall
Feb 28, 2019·Carcinogenesis·Chao YangChun-Sheng Kang
Aug 21, 2018·Frontiers in Cellular and Infection Microbiology·María S Mendoza-FigueroaJesús Valdés
Jul 20, 2018·Frontiers in Cellular and Infection Microbiology·Jesús ValdésMaría S Mendoza-Figueroa
Feb 8, 2021·Nucleic Acids Research·Jana KrálovičováIgor Vořechovský
Aug 24, 2021·Current Opinion in Immunology·Shen-Ying ZhangJean-Laurent Casanova
Nov 3, 2021·Proceedings of the National Academy of Sciences of the United States of America·Gaëlle J S TalrossJoseph G Gall
Dec 16, 2021·Human Genetics·Anjani KumariMarzena Wojciechowska

❮ Previous
Next ❯

Methods Mentioned

BETA
immunoprecipitation
ChIP
pull-down
RIP
gel filtration
xenograft
PCR
transfection

Software Mentioned

Ingenuity Pathway Analysis
SigmaPlot
QIAGEN
TopHat
Cufflinks

Related Concepts

Related Feeds

Alternative splicing

Alternative splicing a regulated gene expression process that allows a single genetic sequence to code for multiple proteins. Here is that latest research.