As next-generation sequencing continues to explode in popularity, researchers are finding out that nucleic acids are a lot more complex than they ever imagined. One miRNA gene = one miRNA? Nah, that would be too simple. Instead, just like their protein-coding counterparts, miRNA genes can give rise to multiple variants, or isomiRs. Now researchers in China have used next-generation sequencing to probe differences in the isomiR repertoire of women with pre-eclampsia, a serious pregnancy condition characterized by high blood pressure and increased protein in the urine.
The Chinese team profiled isomiRs in placental samples from healthy controls and patients with mild or severe pre-eclampsia. Their findings:
- For all three groups, the team detected several isomiRs for each miRNA gene. In general, the most common variants had 3’ deletions that made them shorter than the canonical 22-nt miRNA.
- Over 30% of isomiRs had additional, non-templated nucleotides at their 3’ ends, the most common addition being a single adenosine. IsomiRs with 3’ additions could be shorter, longer, or the same length as the canonical 22-nt miRNA
- Relative to the canonical miRNA, the 3’ addition variants were expressed at low levels in all three groups. But compared with the pre-eclampsia groups, the normal samples showed higher expression of isomiRs with 3’ additions.
- isomiR abundance differed between normal and disease samples, and between mild and severe pre-eclampsia
Although the researchers don’t know exactly how or why cells add extra nucleotides to miRNA 3’ ends, they speculate that 3’ addition may be an important mechanism for altering miRNA stability or function, as well as a potential biomarker of disease.
Celebrate miRNA diversity at PLoS One, June 2011.