rRNA maturation in eukaryotic cells is a multistage process with several alternative pathways, in which a primary polycistronic transcript is successively cleaved and trimmed, giving rise to normal rRNA precursors, aberrant processing intermediates, and processing by-products. (A) In human cells, 47S precursor is converted to 45S by primary endonucleolytic cleavages at sites 01/A′ and 02 (see also panel B). 45S can then enter one of the three parallel pathways: The major one (represented by solid lines) involves cleavage at site 2 within ITS1, producing 30S and 32S pre-rRNAs. 30S species is processed to 18S through 5′-ETS and ITS1 removal. 32S is cleaved at site 4, generating 12S and 28.5S precursors of 5.8S and 28S mature rRNAs. In the second pathway (represented by dashed lines), 5′-ETS is eliminated first, giving rise to 41S pre-rRNA, followed by cleavage of the latter at site 2. The third pathway (represented by dotted lines) involves 41S cleavage at site E in ITS1, producing 18S-E and 36S precursors. Major endonucleolytic processing events are indicated in ovals. (B) Detailed schemes of 47S primary transcript (upper part), normal processing intermediates (middle part), and mature rRNAs (bottom part), presented in panel A. (C) Apart from regular precursors, inefficient or inaccurate pre-rRNA processing in human cells may result in the appearance of aberrant intermediates, e.g., impaired cleavage at site 01/A′ generates 30SL5 species (upper part), which is normally eliminated by XRN2 5′–3′ exonuclease. Furthermore, endonucleolytic cleavages of pre-rRNAs give rise to processing by-products (bottom part). Most of them, including +1-01/A′, A0-1/A1, E-2, and 4a-4 are removed by XRN2. In turn, RRP6 3′–5′ exonucleolytic subunit of the exosome complex has been previously identified as a factor involved in the elimination of 01/A′–A0 species. (D) A scheme of the yeast 35S primary transcript and processing by-products arising during rRNA maturation. Enzymes involved in the degradation of these intermediates are indicated.
