Scheme depicting the experimental approach and HD adapters. a Data were generated to analyse the sequence preferences of T4 Rnl1 and T4 Rnl2 using a degenerate RNA library (N21 RNA). b HD adapters include degenerate tags at the end of the adapters that allow the formation of stable secondary structures for more sequences and reduce RNA ligase-dependent sequence bias. Panel (c) shows the structure of miR-29b with the Illumina adapters (top) and some of the structures formed by HD adapters (bottom). We found 1,031 distinct structures originating from 12,479 tag combinations.