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Publication : Bias in recent miRBase annotations potentially associated with RNA quality issues.

First Author  Ludwig N Year  2017
Journal  Sci Rep Volume  7
Issue  1 Pages  5162
PubMed ID  28701729 Mgi Jnum  J:252931
Mgi Id  MGI:5927118 Doi  10.1038/s41598-017-05070-0
Citation  Ludwig N, et al. (2017) Bias in recent miRBase annotations potentially associated with RNA quality issues. Sci Rep 7(1):5162
abstractText  Although microRNAs are supposed to be stable in-vivo, degradation processes potentially blur our knowledge on the small oligonucleotides. We set to quantify the effect of degradation on microRNAs in mouse to identify causes for distorted microRNAs patterns. In liver, we found 298, 99 and 8 microRNAs whose expression significantly correlated to RNA integrity, storage time at room temperature and storage time at 4 degrees C, respectively. Expression levels of 226 microRNAs significantly differed between liver samples with high RNA integrity compared to liver samples with low RNA integrity by more than two-fold. Especially the 157 microRNAs with increased expression in tissue samples with low RNA integrity were most recently added to miRBase. Testing potentially confounding sources, e.g. in-vitro degraded RNA depleted of small RNAs, we detected signals for 350 microRNAs, suggesting cross-hybridization of fragmented RNAs. Therefore, we conclude that especially microRNAs added in the latest miRBase versions might be artefacts due to RNA degradation. The results facilitate differentiation between degradation-resilient microRNAs, degradation-sensitive microRNAs, and likely erroneously annotated microRNAs. The latter were largely identified by NGS but not experimentally validated and can severely bias microRNA biomarker research and impact the value of microRNAs as diagnostic, prognostic or therapeutic tools.
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