The IRP/IRE regulatory system, pivotal in post-transcriptional cellular iron control, comprises iron-responsive elements (IREs) – mRNA cis-acting motifs interacting with iron regulatory proteins (IRP1 and IRP2). Despite its early characterization (Hentze MW, et al. Science. 1987), this regulatory system remains a focal point of interest across various biological disciplines.
In this context, we present the latest version of the Searching for Iron Elements web server, SIREs version 3.0, designed for predicting IREs based on sequence input. This update introduces two user-friendly modes that allow easy queries from NCBI and Ensembl using an accession number, along with an expanded set of apical loop motifs for efficient screening. SIREs 3.0 also provides the IRE location within transcripts and details on distance to RNA cap, start and end codons, all of them features that have been proposed to affect the functionality of putative IREs. Additionally, this version introduces a visual reference to aid in comparing predicted scores and free energies with canonical IREs, and a refined score system that accounts for fine-grained sequence and structural considerations based on experimental data.
To ensure continued maintenance, future updates and integration with other services, SIREs 3.0 has been migrated to Python. Finally, a renewed web interface has been implemented to provide a friendly user experience.
With these improvements, SIREs 3.0 is set to offer more comprehensive predictions, reaching a broader audience and providing valuable support to the iron community. SIREs 3.0 is accessible at http://sires-webserver.eu
Supported by grants PID2021-122436OB-I00 from MCIN/AEI /10.13039/501100011033 to MS