Distributive O-GlcNAcylation on the Highly Repetitive C-Terminal Domain of RNA Polymerase II

Biochemistry
Lei LuJiaoyang Jiang

Abstract

O-GlcNAcylation is a nutrient-responsive glycosylation that plays a pivotal role in transcriptional regulation. Human RNA polymerase II (Pol II) is extensively modified by O-linked N-acetylglucosamine (O-GlcNAc) on its unique C-terminal domain (CTD), which consists of 52 heptad repeats. One approach to understanding the function of glycosylated Pol II is to determine the mechanism of dynamic O-GlcNAcylation on the CTD. Here, we discovered that the Pol II CTD can be extensively O-GlcNAcylated in vitro and in cells. Efficient glycosylation requires a minimum of 20 heptad repeats of the CTD and more than half of the N-terminal domain of O-GlcNAc transferase (OGT). Under conditions of saturated sugar donor, we monitored the attachment of more than 20 residues of O-GlcNAc to the full-length CTD. Surprisingly, glycosylation on the periodic CTD follows a distributive mechanism, resulting in highly heterogeneous glycoforms. Our data suggest that initial O-GlcNAcylation can take place either on the proximal or on the distal region of the CTD, and subsequent glycosylation occurs similarly over the entire CTD with nonuniform distributions. Moreover, removal of O-GlcNAc from glycosylated CTD is also distributive and is independent of O-Glc...Continue Reading

References

Mar 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·A K Benson, W G Haldenwang
Dec 14, 2004·The Journal of Biological Chemistry·Karim-Jean ArmachePatrick Cramer
Jun 21, 2005·Genes & Development·Anton MeinhartPatrick Cramer
May 22, 2009·Proceedings of the National Academy of Sciences of the United States of America·Henrik SpåhrRoger D Kornberg
Feb 9, 2011·Proceedings of the National Academy of Sciences of the United States of America·Michael BoyceCarolyn R Bertozzi
Jul 12, 2011·Journal of the American Chemical Society·Matthew R LevengoodLaura L Kiessling
Jan 24, 2012·Nature Chemical Biology·Jessica E RexachLinda C Hsieh-Wilson
Apr 24, 2012·Nature Reviews. Molecular Cell Biology·John A HanoverDona C Love
May 19, 2012·The Journal of Biological Chemistry·Stella M RanuncoloBrian A Lewis
Sep 18, 2012·Biochimica Et Biophysica Acta·Martin HeidemannDirk Eick
Oct 3, 2012·Genes & Development·Jing-Ping Hsin, James L Manley
Jul 11, 2013·Chemical Reviews·Célia JeronimoFrançois Robert
Aug 21, 2013·Chemical Reviews·Dirk Eick, Matthias Geyer
Sep 17, 2013·Molecular Cell·Hyunsuk SuhStephen Buratowski
Oct 1, 2013·Biochimica Et Biophysica Acta·Brian A Lewis
Oct 15, 2013·Journal of Cellular Physiology·Giuliana NapolitanoBarbara Majello
Dec 21, 2013·Technology in Cancer Research & Treatment·Yelin SuhPaul J Keall
Jan 30, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·S D YogeshaYan Zhang
Mar 4, 2014·Journal of the American Chemical Society·Rodrigo F Ortiz-MeozSuzanne Walker
Mar 7, 2014·Clinical Proteomics·Junfeng Ma, Gerald W Hart
Oct 23, 2014·The Journal of Biological Chemistry·Brian A Lewis, John A Hanover
Apr 1, 2015·The Journal of Cell Biology·Michelle R Bond, John A Hanover
Aug 4, 2015·Nature Structural & Molecular Biology·Shalini PathakDaan M F van Aalten
Dec 19, 2015·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·C A Rodriguez, M Martín

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Citations

Jun 4, 2016·Molecular Cell·Jean-Pierre Etchegaray, Raul Mostoslavsky
Sep 9, 2016·Nature Structural & Molecular Biology·Justyna ZaborowskaShona Murphy
Jan 6, 2017·ACS Chemical Biology·Matthew WorthJiaoyang Jiang
Mar 2, 2017·Nature Reviews. Molecular Cell Biology·Kevin M Harlen, L Stirling Churchman
Mar 30, 2018·Journal of Bioenergetics and Biomembranes·John A HanoverMichelle R Bond
May 3, 2018·The FEBS Journal·Saar A M van der LaarseAlbert J R Heck
May 14, 2020·Transcription·Danielle E LyonsMelanie Ott
May 24, 2017·Cellular and Molecular Life Sciences : CMLS·Xiaofeng MaJunwei Hao
Sep 27, 2018·Frontiers in Endocrinology·Michael W KrauseJohn A Hanover
Nov 22, 2019·ACS Chemical Biology·Liubov Yakovlieva, Marthe T C Walvoort
Jan 9, 2021·Chemical Reviews·Junfeng MaGerald W Hart
Jul 31, 2020·Physiological Reviews·John C ChathamAdam R Wende
Mar 27, 2021·Biochemical Society Transactions·Yi Zhu, Gerald W Hart
Aug 3, 2021·Chemical Society Reviews·Abhijit SahaAlberto Fernández-Tejada
Jan 7, 2021·ACS Chemical Biology·Liubov YakovlievaMarthe T C Walvoort

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