PMID: 6964391Oct 1, 1982Paper

Transcription initiation by RNA polymerase II is inhibited by S-adenosylhomocysteine

Proceedings of the National Academy of Sciences of the United States of America
R Jove, J L Manley

Abstract

Most eukaryotic mRNAs are blocked at their 5' termini by guanylylation and methylation. These "cap structures" have been shown to play important roles in increasing the stability and translatability of mRNAs. Previous in vitro and in vivo data suggest that these modifications occur extremely early in the synthesis of RNA transcripts by RNA polymerase II. Here we show that S-adenosylhomocysteine (AdoHcy), both a product and an inhibitor of transmethylation reactions, inhibits transcription initiation by RNA polymerase II, but not by RNA polymerase III, in a HeLa whole-cell lysate. AdoHcy must be present during initiation to inhibit transcription and does not affect elongation by RNA polymerase II or the stability of the resultant transcript. Furthermore, AdoHcy does not inhibit transcription by purified HeLa RNA polymerase II. These results suggest that formation of the 5'-cap structure is coupled to initiation of transcription and is consistent with a close association between the capping enzymes and RNA polymerase II at the time of initiation.

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Citations

Jan 1, 1992·Pharmacology & Therapeutics·R ReddyS Shimba
Feb 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·I Grummt, J A Skinner
Nov 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·E D Lewis, J L Manley
Jun 11, 1987·Nucleic Acids Research·D S GrassJ L Manley
Oct 7, 2009·Molecular and Cellular Biology·Maria Elena Fernandez-SanchezVictoria H Cowling
Nov 6, 2007·Proceedings of the National Academy of Sciences of the United States of America·Syuzo KanekoJames L Manley
Apr 26, 2008·Current Opinion in Cell Biology·Shatakshi PanditXiang-Dong Fu
May 12, 2015·Molecular Cell·Fuensanta W Martinez-RucoboPatrick Cramer
Mar 27, 2012·Wiley Interdisciplinary Reviews. RNA·Xavier Roca, Fedor V Karginov
Dec 23, 2009·The Biochemical Journal·Victoria H Cowling
Feb 18, 2004·Molecular Cell·Stephanie C SchroederDavid Bentley
Nov 7, 2002·Molecular Cell·Lawrence C MyersPaul Tempst
Feb 18, 2010·Structure·Meigang GuChristopher D Lima
Jan 12, 2017·The Journal of Antibiotics·Masayuki IgarashiAkio Nomoto

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