MiRNAmotif—A Tool for the Prediction of Pre-miRNA–Protein Interactions

Martyna Urbanek-Trzeciak,Edyta Jaworska,Wlodzimierz Krzyzosiak

doi:10.3390/ijms19124075

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.

Highlights

MicroRNAs are short, non-coding post-transcriptional gene regulators that control many fundamental cellular processes, such as metabolism, cellular proliferation, apoptosis, immune function, epigenetics, and neurodevelopment [1,2]
To show the applicability of the miRNAmotif tool for specific biological problems, we analyzed publicly available data to identify pre-miRNAs that may be regulated by Lin28 (Section 2.1.1), MCPIP1, and DGCR8 (Section 2.1.2), and to find the motifs that are potentially recognized by the DDX1 and DDX17 proteins (Section 2.2.1)
In the linking sequence search, we showed that in addition to these two miRNAs, the GGAG motif was found in other miRNAs from the let-7 family: hsa-let-7a-1, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-let-7g, and hsa-let-7i

Summary

Introduction

MicroRNAs (miRNAs) are short, non-coding post-transcriptional gene regulators that control many fundamental cellular processes, such as metabolism, cellular proliferation, apoptosis, immune function, epigenetics, and neurodevelopment [1,2]. Most mammalian miRNAs are produced in the canonical miRNA biogenesis pathway. This pathway includes the excision of mature miRNA from the primary transcript (pri-miRNA) by sequential nuclear (Microprocessor complex-mediated) and cytoplasmic (Dicer-mediated) processing through the intermediate miRNA precursor (pre-miRNA) [14,15,16]. Increasing numbers of other cellular proteins and RNAs (including long non-coding RNAs) are shown to influence miRNA biogenesis and function [17,18,19,20], adding to the complexity of the miRNA pathway. Some of the RNA-binding proteins (RBPs) known to bind mRNAs can interact with miRNA precursors, creating indirect crosstalk between mRNA and miRNA [21]

Methods

Results

Conclusion