Terminal Adenosyl Transferase Activity of Posttranscriptional Regulator HuR Revealed by Confocal On-Bead Screening

Nicole-Claudia Meisner, Martin Hintersteiner, Jan-Marcus Seifert, Roman Bauer, Roger Marc Benoit, Armin Widmer, Torsten Schindler, Volker Uhl, Michaela Lang, Hubert Gstach, Manfred Auer

Research output: Contribution to journalArticlepeer-review

Abstract

Posttranscriptional regulation and RNA metabolism have become central topics in the understanding of mammalian gene expression and cell signalling, with the 3' untranslated region emerging as the coordinating unit. The 3' untranslated region trans-acting factor Hu protein R (HuR) forms a central posttranscriptional pathway node bridging between AU-rich element-mediated processes and microRNA regulation. While (m)RNA control by HuR has been extensively characterized, the molecular mode of action still remains elusive. Here we describe the identification of the first RRM3 (RNA recognition motif 3) targeted low molecular weight HuR inhibitors from a one-bead-one-compound library screen using confocal nanoscanning. A further compound characterization revealed the presence of an ATP-binding pocket within HuR RRM3, associated with enzymatic activity. Centered around a metal-ion-coordinating DxD motif, the catalytic site mediates 3'-terminal adenosyl modification of non-polyadenylated RNA substrates by HuR. These findings suggest that HuR actively contributes to RNA modification and maturation and thereby shed an entirely new light on the role of HuR in RNA metabolism. (C) 2009 Published by Elsevier Ltd.

Original languageEnglish
Pages (from-to)435-450
Number of pages16
JournalJournal of Molecular Biology
Volume386
Issue number2
DOIs
Publication statusPublished - 20 Feb 2009

Keywords

  • HuR
  • AU-rich
  • posttranscriptional regulation
  • CONA
  • screening

Fingerprint

Dive into the research topics of 'Terminal Adenosyl Transferase Activity of Posttranscriptional Regulator HuR Revealed by Confocal On-Bead Screening'. Together they form a unique fingerprint.

Cite this