Major pathway of rRNA processing in the nucleolus and cytosol

Stable Identifier
Homo sapiens
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In humans, a 47S precursor rRNA (pre-rRNA) is transcribed by RNA polymerase I from rRNA-encoding genes (rDNA) at the boundary of the fibrillar center and the dense fibrillar components of the nucleolus (Stanek et al. 2001). The 47S precursor is processed over the course of about 5-8 minutes (Popov et al. 2013) by endoribonucleases and exoribonucleases to yield the 28S rRNA and 5.8S rRNA of the 60S subunit and the 18S rRNA of the 40S subunit (reviewed in Mullineus and Lafontaine 2012, Henras et al. 2015). As the pre-rRNA is being transcribed, a large protein complex, the small subunit (SSU) processome, assembles in the region of the 18S rRNA sequence, forming terminal knobs on the pre-rRNA (reviewed in Phipps et al. 2011, inferred from yeast in Dragon et al. 2002). The SSU processome contains both ribosomal proteins of the small subunit and processing factors which process the pre-rRNA and modify nucleotides. Through addition of subunits the SSU processome appears to be converted into the larger 90S pre-ribosome (inferred from yeast in Grandi et al. 2002). An analogous large subunit processome (LSU) assembles in the region of the 28S rRNA, however the LSU is less well characterized (inferred from yeast in McCann et al. 2015).
Following cleavage of the pre-rRNA within internal transcribed spacer 1 (ITS1), the pre-ribosomal particle separates into a pre-60S subunit and a pre-40S subunit in the nucleolus (reviewed in Hernandez-Verdun et al. 2010, Phipps et al. 2011). The pre-60S and pre-40S ribosomal particles are then exported from the nucleus to the cytoplasm where the processing factors dissociate and recycle back to the nucleus
Nuclease digestions of the 47S pre-rRNA can follow several paths. In the major pathway, the ends of the 47S pre-rRNA are trimmed to yield the 45S pre-rRNA. Digestion at site 2 (also called site 2b in mouse, see Henras et al. 2015 for nomenclature) cleaves the 45S pre-rRNA to yield the 30S pre-rRNA containing the 18S rRNA of the small subunit and the 32S pre-rRNA containing the 5.8S rRNA and the 28S rRNA of the large subunit. The 32S pre-rRNA is digested in the nucleus to yield the 5.8S rRNA and the 28S rRNA while the 30S pre-rRNA is digested in the nucleus to yield the 18SE pre-rRNA which is then processed in the nucleus and cytosol to yield the 18S rRNA. At least 286 human proteins, 74 of which have no yeast homolog, are required for efficient processing of pre-rRNA in the nucleus (Tafforeau et al. 2013)

Literature References
PubMed ID Title Journal Year
11862453 Non-isotopic mapping of ribosomal RNA synthesis and processing in the nucleolus

Stanek, D, Pliss, A, Malínský, J, Risueño, MC, Raska, I, Masata, M, Koberna, K, Vecerová, J

Chromosoma 2001
23412654 Duration of the first steps of the human rRNA processing

Popov, A, Raska, I, Raška, O, Kováčik, L, Hagen, G, Stixová, L, Smirnov, E

Nucleus 2013
21318072 The small subunit processome in ribosome biogenesis—progress and prospects

Charette, JM, Phipps, KR, Baserga, SJ

Wiley Interdiscip Rev RNA 2011
22342225 Mapping the cleavage sites on mammalian pre-rRNAs: where do we stand?

Mullineux, ST, Lafontaine, DL

Biochimie 2012
25346433 An overview of pre-ribosomal RNA processing in eukaryotes

O'Donohue, MF, Plisson-Chastang, C, Chakraborty, A, Henras, AK, Gleizes, PE

Wiley Interdiscip Rev RNA 2015
12150911 90S pre-ribosomes include the 35S pre-rRNA, the U3 snoRNP, and 40S subunit processing factors but predominantly lack 60S synthesis factors

Strauss, D, Marzioch, M, Tschochner, H, Grandi, P, Tollervey, D, Petfalski, E, Hurt, E, Rybin, V, Bassler, J, Kuster, B, Schäfer, T, Gavin, AC

Mol. Cell 2002
21956940 The nucleolus: structure/function relationship in RNA metabolism

Hernandez-Verdun, D, Thiry, M, Roussel, P, Sirri, V, Lafontaine, DL

Wiley Interdiscip Rev RNA 2010
23973377 The complexity of human ribosome biogenesis revealed by systematic nucleolar screening of Pre-rRNA processing factors

Mullineux, ST, Stamatopoulou, V, Zorbas, C, Langhendries, JL, Wacheul, L, Mullier, R, Lafontaine, DL, Tafforeau, L

Mol. Cell 2013
12068309 A large nucleolar U3 ribonucleoprotein required for 18S ribosomal RNA biogenesis

Compagnone-Post, PA, Shabanowitz, J, Wehner, KA, Wormsley, S, Baserga, SJ, Mitchell, BM, Osheim, Y, Gallagher, JE, Porwancher, KA, Settlage, RE, Dragon, F, Hunt, DF, Beyer, AL

Nature 2002
25877921 A protein interaction map of the LSU processome

Charette, JM, Baserga, SJ, McCann, KL, Vincent, NG

Genes Dev. 2015
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