While microRNAs have been generally thought of as very homogenous little genomic modulators, some new studies are finding that there is actually an entire miRNA cosmos out there with slight variations that are relevant to gender and population differences in mammals. Over at Thomas Jefferson University, Isidore Rigoutsos and his colleagues have already seen some pretty far out mammalian events, including 5′ UTR targeting and individual differences in the miRNA targetome across tissues. Now their molecular observatory has spotted some interesting microRNA isoform dependecies.
By characterizing expression profiles in human lymphoblastoid cell lines of 452 men and women from five different population groups using Argonaute PAR-CLIP they noticed:
- Expression dependecies, manifesting at the level of population and gender, and leading to specific miRNA isoforom expression, which they coined as ‘isomiRs’.
- Interestingly, for each identified isomiR, the abundance remained consistent across their biological replicates, indicating that their observations are not degradation products.
- isomiR sequence differs from known miRNA sequence at either the 5′ end, the 3´ end, or both.
- These alterations can lead to different ‘seed’ sequences and suggest a different targetome for each isomiR, thus adding even more layers to the complexity of miRNA regulation.
From a technological perspective, they have a functional strength to their observations since PAR-CLIP shows which isomiRs are ‘locked and loaded’ into the Argonaute silencing complex. So now it seems that miRNAs aren’t a “single entity with fixed endpoints ” but rather a much more dynamic beast in nature that allows for molecular variation at the level of population and gender.
Check out the vast targetome cosmos in Oncotarget, September 2014