Impact of mutational signatures on microRNA and their response elements.

MicroRNAs are a class of small non-coding RNA molecules with great importance for regulating a large number of diverse biological processes in health and disease, mostly by binding to complementary microRNA response elements (MREs) on protein-coding messenger RNAs and other non-coding RNAs and subsequently inducing their degradation. A growing body of evidence indicates that the dysregulation of certain microRNAs may either drive or suppress oncogenesis.The seed region of a microRNA is of crucial importance for its target recognition. Mutations in these seed regions may disrupt the binding of microRNAs to their target genes. In this study, we investigate the theoretical impact of cancer-associated mutagenic processes and their mutational signatures on microRNA seeds and their MREs. To our knowledge, this is the first study which provides a probabilistic framework for microRNA and MRE sequence alteration analysis based on mutational signatures and computationally assessing the disruptive impact of mutational signatures on human microRNA-target interactions.