Pre-rRNA processing pathways in HeLa cells. The sequences of the mature 18S, 5.8S, and 28S rRNAs are flanked by external transcribed spacers (5′-ETS and 3′-ETS) and separated by internal transcribed spacers (ITS1 and ITS2) in the 45S primary transcript. Numbers above the 45S pre-rRNA indicate cleavage sites. Temporal order of cleavage at sites 1 and 2 defines the 2 pre-rRNA processing pathways represented here. The major pathway A is characterized by production of the 41S precursor by early removal of the 5′-ETS. The 41S species is then cleaved in the ITS1 sequence to generate the 21S and 32S species that are precursors to the RNA components of the large and small ribosomal subunits, respectively. Arrows indicate the cleavage sites. Nomenclature of the pre-RNAs according to Hadjiolova et al²³  and Rouquette et al.²⁴