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miRNAmotif-A Tool for the Prediction of Pre-miRNA⁻Protein Interactions
Martyna O Urbanek-Trzeciak1, Edyta Jaworska2, Wlodzimierz J Krzyzosiak3
1Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland. martyna.urbanek@gmail.com.
Abstract:
MicroRNAs (miRNAs) are short, non-coding post-transcriptional gene regulators. In mammalian cells, mature miRNAs are produced from primary precursors (pri-miRNAs) using canonical protein machinery, which includes Drosha/DGCR8 and Dicer, or the non-canonical mirtron pathway. In plant cells, mature miRNAs are excised from pri-miRNAs by the DICER-LIKE1 (DCL1) protein complex. The involvement of multiple regulatory proteins that bind directly to distinct miRNA precursors in a sequence- or structure-dependent manner adds to the complexity of the miRNA maturation process. Here, we present a web server that enables searches for miRNA precursors that can be recognized by diverse RNA-binding proteins based on known sequence motifs to facilitate the identification of other proteins involved in miRNA biogenesis. The database used by the web server contains known human, murine, and Arabidopsis thaliana pre-miRNAs. The web server can also be used to predict new RNA-binding protein motifs based on a list of user-provided sequences. We show examples of miRNAmotif applications, presenting precursors that contain motifs recognized by Lin28, MCPIP1, and DGCR8 and predicting motifs within pre-miRNA precursors that are recognized by two DEAD-box helicases-DDX1 and DDX17. miRNAmotif is released as an open-source software under the MIT License. The code is available at GitHub (www.github.com/martynaut/mirnamotif). The webserver is freely available at http://mirnamotif.ibch.poznan.pl.
Insights
This study introduces miRNAmotif, a web server for identifying RNA-binding proteins that recognize microRNA precursors. It aids in discovering new proteins involved in microRNA biogenesis using known sequence motifs.
Area of Science:
- Molecular Biology
- Bioinformatics
- Genetics
Background:
- MicroRNAs (miRNAs) are crucial gene regulators, with their maturation involving complex protein interactions with precursor molecules.
- Both canonical (Drosha/DGCR8, Dicer) and non-canonical pathways, as well as plant-specific DICER-LIKE1 (DCL1), process primary miRNAs (pri-miRNAs).
- Sequence- and structure-specific binding of regulatory proteins to miRNA precursors adds significant complexity to miRNA biogenesis.
Purpose of the Study:
- To develop a web server, miRNAmotif, for identifying miRNA precursors bound by RNA-binding proteins based on known sequence motifs.
- To facilitate the discovery of novel proteins involved in microRNA biogenesis.
- To provide a tool for predicting new RNA-binding protein motifs from user-provided sequences.
Main Methods:
- Development of a web server (miRNAmotif) utilizing a database of known human, murine, and *Arabidopsis thaliana* pre-miRNAs.
- Implementation of motif searching based on known sequence patterns.
- Inclusion of functionality for predicting novel RNA-binding protein motifs from user-submitted sequences.
Main Results:
- The web server successfully identifies pre-miRNAs containing motifs for known proteins like Lin28, MCPIP1, and DGCR8.
- The tool predicted motifs for DEAD-box helicases DDX1 and DDX17 within pre-miRNA sequences.
- miRNAmotif is available as open-source software with its code accessible on GitHub.
Conclusions:
- miRNAmotif provides a valuable resource for exploring RNA-binding protein interactions with miRNA precursors.
- The tool can accelerate the identification of new regulators in miRNA biogenesis across different species.
- The open-source nature and web accessibility of miRNAmotif promote its widespread use in biological research.
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