PMID- 23663784 OWN - NLM STAT- MEDLINE DCOM- 20130716 LR - 20161125 IS - 1097-4172 (Electronic) IS - 0092-8674 (Linking) VI - 153 IP - 4 DP - 2013 May 9 TI - Roquin promotes constitutive mRNA decay via a conserved class of stem-loop recognition motifs. PG - 869-81 LID - S0092-8674(13)00457-1 [pii] LID - 10.1016/j.cell.2013.04.016 [doi] AB - Tumor necrosis factor-alpha (TNF-alpha) is the most potent proinflammatory cytokine in mammals. The degradation of TNF-alpha mRNA is critical for restricting TNF-alpha synthesis and involves a constitutive decay element (CDE) in the 3' UTR of the mRNA. Here, we demonstrate that the CDE folds into an RNA stem-loop motif that is specifically recognized by Roquin and Roquin2. Binding of Roquin initiates degradation of TNF-alpha mRNA and limits TNF-alpha production in macrophages. Roquin proteins promote mRNA degradation by recruiting the Ccr4-Caf1-Not deadenylase complex. CDE sequences are highly conserved and are found in more than 50 vertebrate mRNAs, many of which encode regulators of development and inflammation. In macrophages, CDE-containing mRNAs were identified as the primary targets of Roquin on a transcriptome-wide scale. Thus, Roquin proteins act broadly as mediators of mRNA deadenylation by recognizing a conserved class of stem-loop RNA degradation motifs. CI - Copyright (c) 2013 Elsevier Inc. All rights reserved. FAU - Leppek, Kathrin AU - Leppek K AD - Helmholtz Junior Research Group Posttranscriptional Control of Gene Expression, German Cancer Research Center, DKFZ-ZMBH Alliance, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. FAU - Schott, Johanna AU - Schott J FAU - Reitter, Sonja AU - Reitter S FAU - Poetz, Fabian AU - Poetz F FAU - Hammond, Ming C AU - Hammond MC FAU - Stoecklin, Georg AU - Stoecklin G LA - eng SI - GEO/GSE44775 PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Cell JT - Cell JID - 0413066 RN - 0 (3' Untranslated Regions) RN - 0 (RNA, Messenger) RN - 0 (Repressor Proteins) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (roquin-2 protein, mouse) RN - EC 2.3.2.27 (Rc3h1 protein, mouse) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) SB - IM MH - 3' Untranslated Regions MH - Animals MH - Base Sequence MH - Cell Line MH - Humans MH - Inflammation/metabolism MH - Macrophages/*metabolism MH - Mice MH - Molecular Sequence Data MH - Nucleic Acid Conformation MH - Nucleotide Motifs MH - *RNA Stability MH - RNA, Messenger/chemistry MH - Repressor Proteins/*metabolism MH - Sequence Alignment MH - Tumor Necrosis Factor-alpha/*genetics MH - Ubiquitin-Protein Ligases/*metabolism EDAT- 2013/05/15 06:00 MHDA- 2013/07/17 06:00 CRDT- 2013/05/14 06:00 PHST- 2012/01/14 00:00 [received] PHST- 2012/12/07 00:00 [revised] PHST- 2013/04/05 00:00 [accepted] PHST- 2013/05/14 06:00 [entrez] PHST- 2013/05/15 06:00 [pubmed] PHST- 2013/07/17 06:00 [medline] AID - S0092-8674(13)00457-1 [pii] AID - 10.1016/j.cell.2013.04.016 [doi] PST - ppublish SO - Cell. 2013 May 9;153(4):869-81. doi: 10.1016/j.cell.2013.04.016.