AREsite: a database for the comprehensive investigation of AU-rich elements

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.

Interleukin 1β Regulation of the System xc− Substrate-specific Subunit, xCT, in Primary Mouse Astrocytes Involves the RNA-binding Protein HuR

“…These classic pentameric AUUUA sequences (65,66) influence gene expression by serving as binding sites for regulatory RNA-binding proteins (37). Primary among these RNA-binding proteins are the ELAV (embryonic lethal abnormal vision)-like proteins.…”

The Protein Zfand5 Binds and Stabilizes mRNAs with AU-rich Elements in Their 3′-Untranslated Regions

“…More than 4000 human mRNAs contain AREs, which represent as much as 8 -16% of the human protein-coding genes (10,11). AREs are more complex than most cis elements in that there is no single consensus sequence for an ARE, and its number varies among ARE-containing RNAs (ARE-RNAs).…”

Tuning the engine

“…34 In the other branch (3) we scan our UTRs in order to identify cis-elements that may be contained therein. Again, we employ both experimentally validated data (A), coming from IRESite 27 and possibly other sources, and computationally predicted annotations, obtained through UTRsite, 12 AREsite, 26 SIREs 33 and others. Once data collection is completed, we can move to the next step (4): building a network including our initial genes and all the factors identified until this point as regulators.…”

“…Available databases are focused mainly on UTRs annotation, 12,13 RBP-target interactions, 14,15 ncRNAs, [16][17][18][19][20][21][22][23][24] of which miRNAtarget interactions are the greater part, [16][17][18][19][20] with a limited number of resources focusing on lncRNAs, 22,23 and cis-elements. [25][26][27][28][29][30] Furthermore, a small number of resources integrating different data types is available. 12,13,31 Predictive tools also exist, in particular for cis-elements pattern-based search 32,33 and ncRNAs.…”