Abstract
Micro RNAs (miRNAs) (19–25 nucleotides in length) belong to the group of non-coding RNAs are the most abundant group of posttranscriptional regulators in multicellular organisms. They affect a gene expression by binding of fully or partially complementary sequences to the 3’-UTR of target mRNA. Furthermore, miRNAs present a mechanism by which genes with diverse functions on multiple pathways can be simultaneously regulated at the post-transcriptional level. However, little is known about the specific pathways through which miRNAs with specific sequence or structural motifs regulate the cellular processes. In this paper we showed the broad and deep characteristics of mature miRNAs according to their sequence and structural motifs. We investigated a distinct group of miRNAs characterized by the presence of specific sequence motifs, such as UGUGU, GU-repeats and purine/pyrimidine contents. Using computational function and pathway analysis of their targeted genes, we were able to observe the relevance of sequence and the type of targeted mRNAs. As the consequence of the sequence analysis we finally provide the comprehensive description of pathways, biological processes and proteins associated with the distinct group of characterized miRNAs. Here, we found that the specific group of miRNAs with UGUGU can activate the targets associated to the interferon induction pathway or pathways prominently observed during carcinogenesis. GU-rich miRNAs are prone to regulate mostly processes in neurogenesis, whereas purine/pyrimidine rich miRNAs could be involved rather in transport and/or degradation of RNAs. Additionally, we have also analyzed the simple sequence repeats (SSRs). Their variation within mature miRNAs might be critical for normal miRNA regular activity. Expansion or contraction of SSRs in mature miRNA might directly affect its mRNA interaction or even change the function of that distinct miRNA. Our results prove that due to the specific sequence features, these molecules can also be involved in well-defined cellular processes depending on their sequence contents. The pathway mapping and theoretical gene target identification allowed us to create a biological framework to show the relevance of the specific miRNAs in regulation the distinct type of targets.
Highlights
IntroductionRNAs are one of the most structurally and functionally diverse molecular players within the cell
Among all biological macromolecules, RNAs are one of the most structurally and functionally diverse molecular players within the cell
For a very long time, RNA was considered to be exclusively the carrier of genetic information, but the group of RNAs with regulatory function have evolved into the Micro RNAs (miRNAs), long– noncoding RNAs, circular RNAs or miRNA-sponges [71]
Summary
RNAs are one of the most structurally and functionally diverse molecular players within the cell They fulfill many different functions such as coding and transferring genetic information, controlling various cellular processes, as well as catalyzing cleavage reactions, synthesis and ligations [1]. MiRNAs are a class of endogenous, non-coding small RNA, 19–25 nucleotides in length, that mediate the post-transcriptional regulation of mRNAs expression. They are evolutionary conserved, and control diverse biological processes as developmental timing, differentiation, cell proliferation, cancer or neurodegenerative disorders and apoptosis [2,3,4,5,6,7,8,9]. Pronounced occurrence of U at the 5’ end enhances the preference of the strand selection
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