MicroRNA 3' end nucleotide modification patterns and arm selection preference in liver tissues

The expression of microRNA (miRNA) genes undergoes several maturation steps. Recent studies brought new insights into the maturation process, but also raised debates on the maturation mechanism. To understand the mechanism better, we downloaded small RNA sequence reads from NCBI SRA and quantified the expression profiles of miRNAs in normal and tumor liver tissues.

From these miRNA expression profiles, we studied several issues related to miRNA biogenesis. First of all, the 3' ends of mature miRNAs usually carried modified nucleotides, generated from nucleotide addition or RNA editing. We found that adenine accounted for more than 50% of all miRNA 3' end modification events in all libraries. However, uracil dominated over adenine in several miRNA types. Moreover, the miRNA reads in the HBV-associated libraries have much lower rates of nucleotide modification. These results indicate that miRNA 3' end modifications are miRNA specific and may differ between normal and tumor tissues. Secondly, according to the hydrogen-bonding theory, the expression ratio of 5p arm to 3p arm miRNAs, derived from the same pre-miRNA, should be constant over tissues. However, a comparison of the expression profiles of the 5p arm and 3p arm miRNAs showed that one arm is preferred in the normal liver tissue whereas the other is preferred in the tumor liver tissue. In other words, different liver tissues have their own preferences on selecting either arm to be mature miRNAs.

The results suggest that besides the traditional miRNA biogenesis theory, another mechanism may also participate in the miRNA biogenesis pathways.