If variety is the spice of life, then miRNAs are a bowl of 3-alarm Texas chili. A new study in the journal RNA used NextGen sequencing techniques to reveal that miRNAs show quite a bit of sequence variety, even within individual miRNA species.
The research, conducted by Lik Wee Lee and colleagues at the Institute for Systems Biology, used multiple NextGen sequencing platforms to profile miRNAs from 14 human and mouse samples acquired from different types of experiments. The talented ISB team looked at miRNA sequence heterogeneity in their data, and found that many individual miRNAs showed a range of variation, termed isomirs, when aligned back to the genome. Further analysis of their results showed:
- There are significant discrepancies to “known” sequences in public databases
- The most abundant isomirs varied between species and tissue samples
- Mature miRNAs have significant end sequence variation, mostly on the 3’ end
- Distribution of isomirs may be cell-type specific and may have functional implications
The scientists point out that isomirs might also be throwing a monkey wrench into many miRNA measurement techniques. The most popular protocols (microarrays and qRT-PCR) require the use of very specific probes or primers to find their target miRNAs. Any significant sequence variation, like from an isomir, may leave you with inaccurate miRNA profiling data and a queasy feeling in your stomach.
The authors have created an isomir database, and made it available online in the hopes that it may aid others in designing new miRNA detection reagents that can account for isomirs.
Get a handle on all the miRNA variety at RNA, October 2010.