A schematic representation of the impact of cross-links on RNA extraction. In FFPE materials, RNA has been chemically modified by methylol groups to form cross-links with protein. Digestion with proteinase K  followed by column elution is the common method used to extract RNA from FFPE. However, a fraction of RNA remains impervious to extraction because of un-removed cross-links. The longer an RNA molecule is, the more likely cross-links will remain after the digestion procedure. Therefore, it is easier to extract small RNA molecules than larger ones from archival material.