About miRNAs, miRNA seeds, target genes and target pathways

Abstract

miRNAs are typically repressing gene expression by binding to the 3’ UTR, leading to degradation of the mRNA. This process is dominated by the eight-base seed region of the miRNA. Further, miRNAs are known not only to target genes but also to target significant parts of pathways. A logical line of thoughts is: miRNAs with similar (seed) sequence target similar sets of genes and thus similar sets of pathways.By calculating similarity scores for all 3.25 million pairs of 2,550 human miRNAs, we found that this pattern frequently holds, while we also observed exceptions. Respective results were obtained for both, predicted target genes as well as experimentally validated targets. We note that miRNAs target gene set similarity follows a bimodal distribution, pointing at a set of 282 miRNAs that seems to target genes with very high specificity. Further, we discuss miRNAs with different (seed) sequences that nonetheless regulate similar gene sets or pathways. Most intriguingly, we found miRNA pairs that regulate different gene sets but similar pathways such as miR-6886-5p and miR-3529-5p. These are jointly targeting different parts of the MAPK signaling cascade.The main goal of this study is to provide a general overview on the results, to highlight a selection of relevant results on miRNAs, miRNA seeds, target genes and target pathways and to raise awareness for artifacts in respective comparisons. The full set of information that allows to infer detailed results on each miRNA has been included in miRPathDB, the miRNA target pathway database (https://mpd.bioinf.uni-sb.de).

The Relevance of Thimet Oligopeptidase in the Regulation of Energy Metabolism and Diet-Induced Obesity

“…Table 8 shows the amino acid sequences of the 17 identified peptides, their precursor proteins with respective predominant subcellular localization, and the average THOP1 −/− /WT ratios of peptides identified in duplicates from at least three out of the five experimental replicates. These procedures were relevant for increasing data robustness, because the relative concentrations of intracellular peptides varied greatly between the different samples, as previously observed [98]. Most of the peptides identified herein (14 of 17) had altered relative ratios in THOP1 −/− animals compared to WT animals fed an SD (Table 8, colored lanes).…”

Extracellular Vesicle-Contained microRNA of C. elegans as a Tool to Decipher the Molecular Basis of Nematode Parasitism

“…miRNAs from the corresponding mammalian host species were also extracted from miRBase (v. 22): Sus scrofa (n = 457), Mus musculus (n = 1,978), Ovis aries (n = 153), as well as those from C. elegans (n = 437). In order to evaluate seed sequence conservation toward host miRNAs vs. nematode miRNAs, we assessed the proportion of identical seed sequences in parasite vs. host, and in parasite vs. C. elegans in a similarity matrix (Hamming distance), as proposed previously (Kehl et al, 2017). Briefly, the matrices consisted of pairwise comparisons between (i) all parasite and host seeds for each host-parasite association, and (ii) all parasite vs. C. elegans seeds (using 437 C. elegans mature miRNAs from miRBase).…”

microRNA-29b knocks down collagen type I production in cultured rainbow trout (Oncorhynchus mykiss) cardiac fibroblasts

“…The seed sequence of a miR is composed of ∼8 nucleotides within the miRNA sequence and is the main part of the miRNA that is responsible for targeting mRNA (Kehl et al, 2017). To confirm that miR-29b was able to target col1a1 and col1a3, TargetScanFishpredicted binding sites were manually searched for in the generated alignment.…”