Computational Prediction of Functional MicroRNA–mRNA Interactions
Saçar Demirci,, Müşerref D. ; Yousef, Malik ; Allmer, Jens - \ 2019
In: Computational Biology of Non-Coding RNA New York : Springer (Methods in Molecular Biology ) - ISBN 9781493989812 - p. 175 - 196.
Proteins have a strong influence on the phenotype and their aberrant expression leads to diseases. MicroRNAs (miRNAs) are short RNA sequences which posttranscriptionally regulate protein expression. This regulation is driven by miRNAs acting as recognition sequences for their target mRNAs within a larger regulatory machinery. A miRNA can have many target mRNAs and an mRNA can be targeted by many miRNAs which makes it difficult to experimentally discover all miRNA–mRNA interactions. Therefore, computational methods have been developed for miRNA detection and miRNA target prediction. An abundance of available computational tools makes selection difficult. Additionally, interactions are not currently the focus of investigation although they more accurately define the regulation than pre-miRNA detection or target prediction could perform alone. We define an interaction including the miRNA source and the mRNA target. We present computational methods allowing the investigation of these interactions as well as how they can be used to extend regulatory pathways. Finally, we present a list of points that should be taken into account when investigating miRNA–mRNA interactions. In the future, this may lead to better understanding of functional interactions which may pave the way for disease marker discovery and design of miRNA-based drugs.
The expressed MicroRNA-mRNA interactions of Toxoplasma gondii
Acar, Ilhan E. ; Saçar Demirci, Müserref D. ; Groß, Uwe ; Allmer, Jens - \ 2018
Frontiers in Microbiology 8 (2018)JAN. - ISSN 1664-302X
Differential expression - Expression analysis - MicroRNA - MiRNA target - MiRNA-mRNA interactions - Regulation - Toxoplasma gondii
MicroRNAs (miRNAs) are involved in post-transcriptional modulation of gene expression and thereby have a large influence on the resulting phenotype. We have previously shown that miRNAs may be involved in the communication between Toxoplasma gondii and its hosts and further confirmed a number of proposed specific miRNAs. Yet, little is known about the internal regulation via miRNAs in T. gondii. Therefore, we predicted pre-miRNAs directly from the type II ME49 genome and filtered them. For the confident hairpins, we predicted the location of the mature miRNAs and established their target genes. To add further confidence, we evaluated whether the hairpins and their targets were co-expressed. Such co-expressed miRNA and target pairs define a functional interaction. We extracted all such functional interactions and analyzed their differential expression among strains of all three clonal lineages (RH, PLK, and CTG) and between the two stages present in the intermediate host (tachyzoites and bradyzoites). Overall, we found ~65,000 expressed interactions of which ~5,500 are differentially expressed among strains but none are significantly differentially expressed between developmental stages. Since miRNAs and target decoys can be used as therapeutics we believe that the list of interactions we provide will lead to novel approaches in the treatment of toxoplasmosis.