@article{c14f53bebadc4228a6f642347d18bf50,
title = "Structure-Mediated RNA Decay by UPF1 and G3BP1",
abstract = "Post-transcriptional mechanisms regulate the stability and, hence, expression of coding and noncoding RNAs. Sequence-specific features within the 3′ untranslated region (3′ UTR) often direct mRNAs for decay. Here, we characterize a genome-wide RNA decay pathway that reduces the half-lives of mRNAs based on overall 3′ UTR structure formed by base pairing. The decay pathway is independent of specific single-stranded sequences, as regulation is maintained in both the original and reverse complement orientation. Regulation can be compromised by reducing the overall structure by fusing the 3′ UTR with an unstructured sequence. Mutating base-paired RNA regions can also compromise this structure-mediated regulation, which can be restored by re-introducing base-paired structures of different sequences. The decay pathway requires the RNA-binding protein UPF1 and its associated protein G3BP1. Depletion of either protein increased steady-state levels of mRNAs with highly structured 3′ UTRs as well as highly structured circular RNAs. This structure-dependent mechanism therefore enables cells to selectively regulate coding and noncoding RNAs.",
keywords = "3′ untranslated region, G3BP1, RNA base pairing, RNA decay, RNA structure, UPF1, circular RNA",
author = "Fischer, {Joseph W.} and Busa, {Veronica F.} and Yue Shao and Leung, {Anthony K.L.}",
note = "Funding Information: We thank the Leung laboratory, C. Fischer, P. Sharp, R. Green, B. Zinshteyn, H. Dietz, J. Kim, S. Bailey, S. Woodson, G. Seydoux, M. Matunis, S. Myong, and J. Wilusz for discussion and reading the manuscript. We thank the ENCODE Consortium and the G. Yeo laboratory for the G3BP1 eCLIP dataset. We thank N. Kedersha for U2OS G3BP1/2 KO cells and G3BP1-GFP plasmid; L. Maquat for UPF1-FLAG plasmid; A. Holland for DLD-1 cells with integrated Flp-In site; and T. Dawson for SH-SY5Y cells. We thank A. Jaffe for providing the ERCC RNA spike-in reagent and J. Ellenberg for λN constructs. This work was supported by Johns Hopkins Bloomberg School of Public Health Start-up fund (A.K.L.L.), Core Coin Pilot grant from Experimental and Computational Core, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (J.W.F., V.F.B., and A.K.L.L.) through NIH NCI grant P30CA006973 , Brian D. Crawford and Family Research Scholarship (J.W.F.), and NIH grants F31GM125109 (J.W.F.), T32CA009110 (J.W.F.), and T32GM007814 (J.W.F.). Funding Information: We thank the Leung laboratory, C. Fischer, P. Sharp, R. Green, B. Zinshteyn, H. Dietz, J. Kim, S. Bailey, S. Woodson, G. Seydoux, M. Matunis, S. Myong, and J. Wilusz for discussion and reading the manuscript. We thank the ENCODE Consortium and the G. Yeo laboratory for the G3BP1 eCLIP dataset. We thank N. Kedersha for U2OS G3BP1/2 KO cells and G3BP1-GFP plasmid; L. Maquat for UPF1-FLAG plasmid; A. Holland for DLD-1 cells with integrated Flp-In site; and T. Dawson for SH-SY5Y cells. We thank A. Jaffe for providing the ERCC RNA spike-in reagent and J. Ellenberg for ?N constructs. This work was supported by Johns Hopkins Bloomberg School of Public Health Start-up fund (A.K.L.L.), Core Coin Pilot grant from Experimental and Computational Core, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (J.W.F. V.F.B. and A.K.L.L.) through NIH NCI grant P30CA006973, Brian D. Crawford and Family Research Scholarship (J.W.F.), and NIH grants F31GM125109 (J.W.F.), T32CA009110 (J.W.F.), and T32GM007814 (J.W.F.). Conceptualization, J.W.F. and A.K.L.L.; Methodology, J.W.F. V.F.B. Y.S. and A.K.L.L.; Formal Analysis, J.W.F. and V.F.B.; Investigation, J.W.F. V.F.B. and Y.S.; Writing ? Original Draft, J.W.F. and A.K.L.L.; Writing ? Review & Editing, J.W.F. V.F.B. Y.S. and A.K.L.L.; Supervision, A.K.L.L.; Funding Acquisition, J.W.F. V.F.B. and A.K.L.L. Authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = apr,
day = "2",
doi = "10.1016/j.molcel.2020.01.021",
language = "English (US)",
volume = "78",
pages = "70--84.e6",
journal = "Molecular cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "1",
}