Evidence that the Upf1-related molecular motor scans the 3'-UTR to ensure mRNA integrity.

Nucleic Acids Research
Toshiaki ShigeokaYasumasa Ishida

Abstract

Upf1 is a highly conserved RNA helicase essential for nonsense-mediated mRNA decay (NMD), an mRNA quality-control mechanism that degrades aberrant mRNAs harboring premature termination codons (PTCs). For the activation of NMD, UPF1 interacts first with a translation-terminating ribosome and then with a downstream exon-junction complex (EJC), which is deposited at exon-exon junctions during splicing. Although the helicase activity of Upf1 is indispensable for NMD, its roles and substrates have yet to be fully elucidated. Here we show that stable RNA secondary structures between a PTC and a downstream exon-exon junction increase the levels of potential NMD substrates. We also demonstrate that a stable secondary structure within the 3'-untranslated region (UTR) induces the binding of Upf1 to mRNA in a translation-dependent manner and that the Upf1-related molecules are accumulated at the 5'-side of such a structure. Furthermore, we present evidence that the helicase activity of Upf1 is used to bridge the spatial gap between a translation-termination codon and a downstream exon-exon junction for the activation of NMD. Based on these findings, we propose a model that the Upf1-related molecular motor scans the 3'-UTR in the 5'-to-3' ...Continue Reading

References

Jan 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·P BelgraderL E Maquat
Jun 17, 1998·The EMBO Journal·R ThermannA E Kulozik
Aug 26, 1998·Proceedings of the National Academy of Sciences of the United States of America·X SunL E Maquat
Jul 18, 2002·Current Biology : CB·Josée Dostie, Gideon Dreyfuss
Oct 17, 2002·The Journal of Biological Chemistry·Naoyuki UchidaToshiaki Katada
Apr 30, 2003·Molecular Cell·Niels H GehringAndreas E Kulozik
Mar 11, 2004·Proceedings of the National Academy of Sciences of the United States of America·Eishou MatsudaYasumasa Ishida
Mar 26, 2004·Nature Reviews. Molecular Cell Biology·Lynne E Maquat
May 20, 2005·Current Opinion in Cell Biology·Elena Conti, Elisa Izaurralde
Dec 11, 2007·Nature Structural & Molecular Biology·Hala ChamiehHervé Le Hir
Aug 6, 2008·Nature Reviews. Genetics·Olaf Isken, Lynne E Maquat
Feb 5, 2009·Nature Structural & Molecular Biology·Saverio Brogna, Jikai Wen
May 5, 2009·Cell·Niels H GehringMatthias W Hentze
Oct 30, 2010·Cell·J Robert Hogg, Stephen P Goff
Dec 15, 2010·Cell·Carol J Wilusz, Jeffrey Wilusz

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Citations

Dec 25, 2012·Proceedings of the National Academy of Sciences of the United States of America·Eonyoung ParkLynne E Maquat
Nov 28, 2013·Annual Review of Genetics·Maximilian Wei-Lin Popp, Lynne E Maquat
Feb 18, 2014·Cell Reports·Laurence DecourtyCosmin Saveanu
Aug 19, 2015·Cellular and Molecular Life Sciences : CMLS·Tobias FatscherNiels H Gehring
Sep 15, 2012·The Plant Journal : for Cell and Molecular Biology·Zsuzsanna MéraiDániel Silhavy
Oct 6, 2015·Annual Review of Genetics·Feng He, Allan Jacobson
Oct 8, 2015·Trends in Plant Science·Orit Shaul
Jun 13, 2015·AIDS Research and Human Retroviruses·Vincent MocquetPierre Jalinot
Feb 26, 2013·Biochimica Et Biophysica Acta·Christoph SchweingruberOliver Mühlemann
Mar 31, 2015·Nucleic Acids Research·Evgeniya DegtiarOrit Shaul
Mar 27, 2015·Nature Communications·Maximilian W Popp, Lynne E Maquat
Feb 14, 2013·Proceedings of the National Academy of Sciences of the United States of America·Tatsuaki Kurosaki, Lynne E Maquat
May 18, 2016·Trends in Genetics : TIG·Saverio BrognaMarija Petric
Jan 21, 2016·Journal of Cell Science·Tatsuaki Kurosaki, Lynne E Maquat
Feb 23, 2020·International Journal of Molecular Sciences·Jean-Marie LambertJérôme Saulière
Feb 21, 2014·Molecules and Cells·Maximilian Wei-Lin Popp, Lynne E Maquat
Apr 18, 2019·Nature Reviews. Molecular Cell Biology·Tatsuaki KurosakiLynne E Maquat
Sep 4, 2014·Genes & Development·Tatsuaki KurosakiLynne E Maquat

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Methods Mentioned

BETA
transfections
transfection
FACS
immunoprecipitation
pull-down
RNA-immunoprecipitation

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