AREsite: a Database for the Comprehensive Investigation of AU-rich Elements

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2010 Nov 13

PMID 21071424

Citations 98

Authors

Andreas R Gruber

Jorg Fallmann

Franz Kratochvill

Pavel Kovarik

Ivo L Hofacker

Affiliations

Soon will be listed here.

Abstract

AREsite is an online resource for the detailed investigation of AU-rich elements (ARE) in vertebrate mRNA 3'-untranslated regions (UTRs). AREs are one of the most prominent cis-acting regulatory elements found in 3'-UTRs of mRNAs. Various ARE-binding proteins that possess RNA stabilizing or destabilizing functions are recruited by sequence-specific motifs. Recent findings suggest an essential role of the structural mRNA context in which these sequence motifs are embedded. AREsite is the first database that allows to quantify the structuredness of ARE motif sites in terms of opening energies and accessibility probabilities. Moreover, we also provide a detailed phylogenetic analysis of ARE motifs and incorporate information about experimentally validated targets of the ARE-binding proteins TTP, HuR and Auf1. The database is publicly available at: http://rna.tbi.univie.ac.at/AREsite.

Citing Articles

The LSmAD Domain of Ataxin-2 Modulates the Structure and RNA Binding of Its Preceding LSm Domain.

Zhang S, Zhang Y, Chen T, Hu H, Lu C Cells. 2025; 14(5).

PMID: 40072111 PMC: 11898529. DOI: 10.3390/cells14050383.

Cytoplasmic regulation of the poly(A) tail length as a potential therapeutic target.

Fernandez M, Mendez R RNA. 2025; 31(3):402-415.

PMID: 39805658 PMC: 11874964. DOI: 10.1261/rna.080333.124.

Multiple roles for AU-rich RNA binding proteins in the development of haematologic malignancies and their resistance to chemotherapy.

Podszywalow-Bartnicka P, Neugebauer K RNA Biol. 2024; 21(1):1-17.

PMID: 38798162 PMC: 11135835. DOI: 10.1080/15476286.2024.2346688.

Posttranscriptional Events Orchestrate Immune Homeostasis of CD8 T Cells.

Freen-van Heeren J Methods Mol Biol. 2024; 2782:65-80.

PMID: 38622392 DOI: 10.1007/978-1-0716-3754-8_4.

Endothelial Jagged1 levels and distribution are post-transcriptionally controlled by ZFP36 decay proteins.

Sunshine H, Cicchetto A, Kaczor-Urbanowicz K, Ma F, Pi D, Symons C Cell Rep. 2023; 43(1):113627.

PMID: 38157296 PMC: 10884959. DOI: 10.1016/j.celrep.2023.113627.

References

Meisner N, Hackermuller J, Uhl V, Aszodi A, Jaritz M, Auer M . mRNA openers and closers: modulating AU-rich element-controlled mRNA stability by a molecular switch in mRNA secondary structure. Chembiochem. 2004; 5(10):1432-47. DOI: 10.1002/cbic.200400219. View

Hackermuller J, Meisner N, Auer M, Jaritz M, Stadler P . The effect of RNA secondary structures on RNA-ligand binding and the modifier RNA mechanism: a quantitative model. Gene. 2005; 345(1):3-12. DOI: 10.1016/j.gene.2004.11.043. View

Morgenstern B . DIALIGN 2: improvement of the segment-to-segment approach to multiple sequence alignment. Bioinformatics. 1999; 15(3):211-8. DOI: 10.1093/bioinformatics/15.3.211. View

Taylor G, Carballo E, Lee D, Lai W, Thompson M, Patel D . A pathogenetic role for TNF alpha in the syndrome of cachexia, arthritis, and autoimmunity resulting from tristetraprolin (TTP) deficiency. Immunity. 1996; 4(5):445-54. DOI: 10.1016/s1074-7613(00)80411-2. View

Hudson B, Martinez-Yamout M, Dyson H, Wright P . Recognition of the mRNA AU-rich element by the zinc finger domain of TIS11d. Nat Struct Mol Biol. 2004; 11(3):257-64. DOI: 10.1038/nsmb738. View

Bompfunewerer A, Backofen R, Bernhart S, Hertel J, Hofacker I, Stadler P . Variations on RNA folding and alignment: lessons from Benasque. J Math Biol. 2007; 56(1-2):129-44. DOI: 10.1007/s00285-007-0107-5. View

Rabani M, Kertesz M, Segal E . Computational prediction of RNA structural motifs involved in posttranscriptional regulatory processes. Proc Natl Acad Sci U S A. 2008; 105(39):14885-90. PMC: 2567462. DOI: 10.1073/pnas.0803169105. View

Kedde M, Van Kouwenhove M, Zwart W, Vrielink J, Elkon R, Agami R . A Pumilio-induced RNA structure switch in p27-3' UTR controls miR-221 and miR-222 accessibility. Nat Cell Biol. 2010; 12(10):1014-20. DOI: 10.1038/ncb2105. View

Hodson D, Janas M, Galloway A, Bell S, Andrews S, Li C . Deletion of the RNA-binding proteins ZFP36L1 and ZFP36L2 leads to perturbed thymic development and T lymphoblastic leukemia. Nat Immunol. 2010; 11(8):717-24. PMC: 2953641. DOI: 10.1038/ni.1901. View

10.

Halees A, El-Badrawi R, Khabar K . ARED Organism: expansion of ARED reveals AU-rich element cluster variations between human and mouse. Nucleic Acids Res. 2007; 36(Database issue):D137-40. PMC: 2238997. DOI: 10.1093/nar/gkm959. View

11.

Rhead B, Karolchik D, Kuhn R, Hinrichs A, Zweig A, Fujita P . The UCSC Genome Browser database: update 2010. Nucleic Acids Res. 2009; 38(Database issue):D613-9. PMC: 2808870. DOI: 10.1093/nar/gkp939. View

12.

Hao S, Baltimore D . The stability of mRNA influences the temporal order of the induction of genes encoding inflammatory molecules. Nat Immunol. 2009; 10(3):281-8. PMC: 2775040. DOI: 10.1038/ni.1699. View

13.

Bakheet T, Frevel M, Williams B, Greer W, Khabar K . ARED: human AU-rich element-containing mRNA database reveals an unexpectedly diverse functional repertoire of encoded proteins. Nucleic Acids Res. 2000; 29(1):246-54. PMC: 29778. DOI: 10.1093/nar/29.1.246. View

14.

Tafer H, Ameres S, Obernosterer G, Gebeshuber C, Schroeder R, Martinez J . The impact of target site accessibility on the design of effective siRNAs. Nat Biotechnol. 2008; 26(5):578-83. DOI: 10.1038/nbt1404. View

15.

Li X, Quon G, Lipshitz H, Morris Q . Predicting in vivo binding sites of RNA-binding proteins using mRNA secondary structure. RNA. 2010; 16(6):1096-107. PMC: 2874161. DOI: 10.1261/rna.2017210. View

16.

Crooks G, Hon G, Chandonia J, Brenner S . WebLogo: a sequence logo generator. Genome Res. 2004; 14(6):1188-90. PMC: 419797. DOI: 10.1101/gr.849004. View

17.

Bernhart S, Hofacker I, Stadler P . Local RNA base pairing probabilities in large sequences. Bioinformatics. 2005; 22(5):614-5. DOI: 10.1093/bioinformatics/btk014. View

18.

Barreau C, Paillard L, Osborne H . AU-rich elements and associated factors: are there unifying principles?. Nucleic Acids Res. 2006; 33(22):7138-50. PMC: 1325018. DOI: 10.1093/nar/gki1012. View

19.

Ghosh M, Aguila H, Michaud J, Ai Y, Wu M, Hemmes A . Essential role of the RNA-binding protein HuR in progenitor cell survival in mice. J Clin Invest. 2009; 119(12):3530-43. PMC: 2786787. DOI: 10.1172/JCI38263. View

20.

Lu J, Sadri N, Schneider R . Endotoxic shock in AUF1 knockout mice mediated by failure to degrade proinflammatory cytokine mRNAs. Genes Dev. 2006; 20(22):3174-84. PMC: 1635151. DOI: 10.1101/gad.1467606. View