The intricacies of isomiRs: from classification to clinical relevance.

ABSTRACT

MicroRNAs (miRNAs) and isoforms of their archetype, called isomiRs, regulate gene expression via complementary base-pair binding to messenger RNAs (mRNAs). The partially evolutionarily conserved isomiR sequence variations are differentially expressed among tissues, populations, and genders, and between healthy and diseased states. Aiming towards the clinical use of isomiRs as diagnostic biomarkers and for therapeutic purposes, several challenges need to be addressed, including (i) clarification of isomiR definition, (ii) improved annotation in databases with new standardization (such as the mirGFF3 format), and (iii) improved methods of isomiR detection, functional verification, and in silico analysis. In this review we discuss the respective challenges, and highlight the opportunities for clinical use of isomiRs, especially in the light of increasing amounts of next-generation sequencing (NGS) data.