Since the inception of deep sequencing, isomiRs are consistently observed to be produced by most
miRNA genes in a variety of cell types. IsomiRs appear as a variation in length from the canonical
sequence annotated in miRBase, due to an addition or deletion of one or more nucleotides at the
5’ or 3’ ends or both. As the seed sequence is located at the 5’ end of the microRNA, the target
mRNA will be theoretically different. Therefore, 5’isomiRs might potentially target a new set mRNA
compared to their canonical counterpart. This article gives an overview of investigations that explored
the functional potential of isomiRs such as their ability to incorporate into Argonaute protein, the
differential expression of isomiRs in various tissue types and cell lines, and the differences of
mRNA targets between isomiR and its canonical microRNA. In addition, this article provides a
brief introduction of RNA sponges as a potential way to inhibit isomiRs.