@article{71588f87d7bb49a7ac796540d21a79e4,
title = "An RNA guanine quadruplex regulated pathway to TRAIL-sensitization by DDX21",
abstract = "DDX21 is a newly discovered RNA G-quadruplex (rG4) binding protein with no known biological rG4 targets. In this study we used label-free proteomic MS/MS to identify 26 proteins that are expressed at significantly different levels in cells expressing an rG4-binding deficient DDX21 (M4). MS data are available via ProteomeXchange with identifier PXD013501. From this list we validate MAGED2 as a protein that is regulated by DDX21 through rG4 in its 5'-UTR. MAGED2 protein levels, but not mRNA levels, are reduced by half in cells expressing DDX21 M4. MAGED2 has a repressive effect on TRAIL-R2 expression that is relieved under these conditions, resulting in elevated TRAIL-R2 mRNA and protein in MCF-7 cells, rendering them sensitive to TRAIL-mediated apoptosis. Our work identifies the role of DDX21 in regulation at the translational level through biologically relevant rG4 and shows that MAGED2 protein levels are regulated, at least in part, by the potential to form rG4 in their 5'-UTRs.",
keywords = "DDX21, MAGED2, Proteomics, Quadruplex, RNA, TRAIL-R2",
author = "McRae, {Ewan K.S.} and Dupas, {Steven J.} and Booy, {Evan P.} and Piragasam, {Ramanaguru S.} and Fahlman, {Richard P.} and Mckenna, {Sean A.}",
note = "Funding Information: The authors would like to thank Dr. Francis Lin for the use of their lab{\textquoteright}s FACS as well as Dr. Peter Pelka for the use of their lab{\textquoteright}s SpectraMax iD3 plate reader. The authors would also like to thank Jens Kurreck for supplying us with psiCheck 2 vector used in the luciferase assays. This project was funded by the Cancer Research Society (Canada) (20085), CIHR Project Grant (389449) and a Discovery Grant from the Natural Sciences and Engineering Research Council (NSERC) of Canada to R.P.F. E.K.S.M. is supported with funding from NSERC{\textquoteright}s Alexander Graham Bell Canada Graduate Scholarship-Doctoral. Funding Information: The authors would like to thank Dr. Francis Lin for the use of their lab's FACS as well as Dr. Peter Pelka for the use of their lab's SpectraMax iD3 plate reader. The authors would also like to thank Jens Kurreck for supplying us with psiCheck 2 vector used in the luciferase assays. This project was funded by the Cancer Research Society (Canada) (20085), CIHR Project Grant (389449) and a Discovery Grant from the Natural Sciences and Engineering Research Council (NSERC) of Canada to R.P.F. E.K.S.M. is supported with funding from NSERC's Alexander Graham Bell Canada Graduate Scholarship-Doctoral. Publisher Copyright: {\textcopyright} 2020 McRae et al.",
year = "2020",
doi = "10.1261/rna.072199.119",
language = "English (US)",
volume = "26",
pages = "44--57",
journal = "RNA",
issn = "1355-8382",
publisher = "Cold Spring Harbor Laboratory Press",
number = "1",
}