Erythropoietic miR-486-5p and miR-451a depletion from whole blood-derived small RNA sequencing libraries

Erythroid-specific miR-451a and miR-486-5p are two dominant microRNAs (miRNAs) in human peripheral blood-derived small RNA sequencing libraries. Their overabundance reduces diversity as well as complexity of libraries after PCR amplification and consequently causes negative effects such as inaccurate detectability and quantification of other low abundant miRNAs. Here we present a cost-effective and feasible hybridization-based method to deplete these two erythropoietic miRNAs from blood-derived RNA samples. By utilization of blocking oligonucleotides, this method provides highly efficient and specific depletion of miR-486-5p and miR-451a, which leads to a considerable increase of measured expression as well as detectability of low abundant miRNA species. The blocking oligos are compatible with 59 ligation-dependent small RNA library preparation, including commercially available kits, such as Illumina TruSeq and Perkin Elmer NEXTflex protocols.