About

AREsite2 represents an update for AREsite, an on- line resource for the investigation of AU-rich elements (ARE) in human and mouse mRNA 3’UTR sequences.
The new updated and enhanced version allows detailed investigation of AU, GU and U-rich elements (ARE, GRE, URE) in the transcriptome of Homo sapiens, Mus musculus, Danio rerio, Caenorhabditis elegans and Drosophila melanogaster.
It contains information on genomic location, genic context, structuredness and conservation of annotated motifs. Furthermore, we provide a REST interface for experienced users, to interact with the database in an automated manner.

How to query

Select a motif

You can choose the motifs you want to retrieve from the database for the specified gene by selecting them from the list. Alternatively, you can also submit a comma-separated list of motifs in the text field below, if the motif you are looking for is not among the available selection. Please be aware that response time increases with the number of motifs, so only three custom and a total of ten motifs can be queried at once. All images are generated when the first request is made, so if some of the figures are not available in due time, please come back later.

Long queries

For automatic retrieval or long lists of motifs consider using the REST interface via http://rna.tbi.univie.ac.at/AREsite2/api. An example script can be found at: http://rna.tbi.univie.ac.at/AREsite2/bulk.

Species selection

Once you chose your motifs of interest you can select a species to investigate, default is Homo sapiens.

Region of interest

By default, we return only motifs overlapping 3'UTRs, if this is not what you want, change the region of interest to one of the available selections (3'UTR, 5'UTR, CDS, Exon, Intron, All). This is of special importance if you want to screen non-coding, or very long genes!

Gene of interest

At last, enter the name of your gene of interest, ENSEMBL IDs work best, but you can use the gene clear name or any other reference ENSEMBL can resolve, and click submit.

Results

Example output

This section explains example output from AREsite2 for the gene Cxcl2 in homo sapiens.
If a search for the motifs ATTTA, WWTTTWW, GTTTG, TTTGTTT and AWTAAA is started, database entries are provided for the user as svg- plots and html5-tables.
The output begins with information on the genomic location of the searched gene, followed by figure 1A. The latter presents the karyotype of hg38 chromosome 4 with highlighted position of Cxcl2.

Annotation

Figure 1B visualizes the gene body and known transcripts of Cxcl2 as annotated by ENSEMBL. Annotated motifs, colored accordingly, if overlapping experimental data was available (TTP red, Auf1 blue, HuR green, multiple bright red, no overlap gray) are highlighted in fig. 1C.

Conservation

All of these figures contain a link to the ENSEMBL genome browser, where selected motifs are made available as custom tracks. ENSEMBL GERP conservation scores for the whole gene body are visualized in figure 1D where available, if no score is available for a region, it is set to -1.
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Annotated Motifs

The second part of the results sections begins with a table (fig. 2A) providing information on the genomic and genic location of an annoted motif in BED format, as well as experimental evidence for RBP interaction, if available.

Accessibility information

Accessibility information for a 20nt stretch around motifs as well as overlapping stable secondary structures from a genome wide screen, can be seen in the next table (fig. 2B). The structural accessibility plots are interactive svgs, where the span of nucleotides used to calculate accessibility, as well as output in terms of opening energy or probability of being unpaired can be chosen. Each figures can be dowloaded via right click.

Multiple alignments

Detailed conservation information for each motif can be derived as multiple sequence alignment from table three (fig. 2C), if motifs are conservation.

Literature

The concluding table provides the results of the literature search, sorted by newest publications, for up to 100 entries from PubMed (fig. 2D).
All tables are searchable, and entries can be downloaded by the user.
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REST interface

We also provide a REST interface for users with some programming experience. Large or sequential queries are best conducted via this interface. For an example script visit the bulk download section, http://rna.tbi.univie.ac.at/AREsite2/bulk.

Bulk download area

Here you can download annotated motifs for each species as BED, BED12 or GTF, as well as a mysql dump of the whole database (big), and an example perl script for interaction with the REST interface, http://rna.tbi.univie.ac.at/AREsite2/api.

Statistic area

On this page, users can request the number of genes containing a certain motif, for a preselected list. A bar-graph is generated per request, which shows the number of genes which contain the selected motif at least once in following regions: Exon^3UTR, Intron^3UTR, Exon^5UTR, Intron^5UTR, Exon^CDS, Intron^CDS, Exon and Intron.