2013
DOI: 10.1093/nar/gkt160
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Gradual processing of the ITS1 from the nucleolus to the cytoplasm during synthesis of the human 18S rRNA

Abstract: Defects in ribosome biogenesis trigger stress response pathways, which perturb cell proliferation and differentiation in several genetic diseases. In Diamond–Blackfan anemia (DBA), a congenital erythroblastopenia, mutations in ribosomal protein genes often interfere with the processing of the internal transcribed spacer 1 (ITS1), the mechanism of which remains elusive in human cells. Using loss-of-function experiments and extensive RNA analysis, we have defined the precise position of the endonucleolytic cleav… Show more

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Cited by 87 publications
(202 citation statements)
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“…This process was mainly characterized in yeast and, surprisingly, only recently investigated in human cells, revealing that pre-rRNA processing pathways are notably different in metazoan: ∼27% of human factors have distinct or additional functions in pre-rRNA processing compared with their yeast orthologs, and several pre-RNA processing factors have no yeast homolog (26,29). XRN2 (homolog of yeast XRN2/Rat1) plays a major role in rRNA maturation, coordinating the optimal order of multiple pre-rRNA cleavages (25); it is essential for degradation of 5′-extended 45.5S and 34.5S pre-rRNAs forms, it removes ITS-1-derived extensions to generate 32S from 32.5S pre-rRNA, and it promotes decay of 5′-01, 5′-A0, and E2 fragments, generated by endonucleolytic cleavages in the 5′ETS/ITS1 region in human cells (27)(28)(29) (Fig. 4A).…”
Section: Resultsmentioning
confidence: 99%
“…This process was mainly characterized in yeast and, surprisingly, only recently investigated in human cells, revealing that pre-rRNA processing pathways are notably different in metazoan: ∼27% of human factors have distinct or additional functions in pre-rRNA processing compared with their yeast orthologs, and several pre-RNA processing factors have no yeast homolog (26,29). XRN2 (homolog of yeast XRN2/Rat1) plays a major role in rRNA maturation, coordinating the optimal order of multiple pre-rRNA cleavages (25); it is essential for degradation of 5′-extended 45.5S and 34.5S pre-rRNAs forms, it removes ITS-1-derived extensions to generate 32S from 32.5S pre-rRNA, and it promotes decay of 5′-01, 5′-A0, and E2 fragments, generated by endonucleolytic cleavages in the 5′ETS/ITS1 region in human cells (27)(28)(29) (Fig. 4A).…”
Section: Resultsmentioning
confidence: 99%
“…7,8 Thus, there are additional processing sites within human 47S pre-rRNA. [9][10][11] Moreover, in some cases the functions of homologous proteins involved in ribosome synthesis in both species are not equivalent. [12][13][14] Furthermore, alternative pre-rRNA processing pathways are utilized in parallel in both model organisms.…”
Section: Introductionmentioning
confidence: 99%
“…Finally, there are processing events in humans, but not yeast, that occur either through endonucleolytic cleavage or by exoribonucleolytic maturation. 11,16 Processing of human 47S pre-rRNA begins with primary cleavage at site A 0 (also known as 01) in the 5 0 -ETS, which encompasses endoribonucleolytic cleavage sites at 2 adjacent regions between nucleotides 414 and 422 (Fig. 1A).…”
Section: Introductionmentioning
confidence: 99%
“…Ce dernier clivage a lieu dans le cytoplasme. De la même manière que pour le 21S, le pré-ARNr 18S-E subit un rognage 3'-5' préalablement au clivage au site 3 [18]. D'autre part, le pré-ARNr 32S est clivé au site 3' dans l'ITS2, générant l'ARNr mature 28S et le pré-ARNr 12S.…”
Section: Export Des Pré-ribosomesunclassified
“…Ces derniers suivent alors les étapes de clivage décrites précédemment. Dans certaines conditions, le clivage au niveau de l'ITS1 se produit au site E plutôt qu'au site 2 [17,18], générant alors le pré-ARNr 18S-E et un précurseur appelé 36S ( Figure 2C Certains facteurs d'assemblage servent d'adaptateurs pour recruter les exportines et ont ainsi un rôle dans le contrôle de qualité. Dans le cas des précurseurs de la grande sous-unité, c'est la protéine NMD3 qui recrute l'exportine CRM1 (chromosome region maintenance 1; also referred to as exportin1 or Xpo1) [24], et, pour les pré-40S, ce sont les facteurs d'assemblage RIOK2 (RIO kinase 2) et TSR1 qui seraient requis pour lier CRM1 [16,25].…”
Section: Export Des Pré-ribosomesunclassified