Nucleolin Functions in the First Step of Ribosomal RNA Processing

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 1998 Apr 18

PMID 9482744

Citations 152

Authors

H Ginisty

F Amalric

P Bouvet

Affiliations

Soon will be listed here.

Abstract

The first processing step of precursor ribosomal RNA (pre-rRNA) involves a cleavage within the 5' external transcribed spacer. This processing requires sequences downstream of the cleavage site which are perfectly conserved among human, mouse and Xenopus and also several small nucleolar RNAs (snoRNAs): U3, U14, U17 and E3. In this study, we show that nucleolin, one of the major RNA-binding proteins of the nucleolus, is involved in the early cleavage of pre-rRNA. Nucleolin interacts with the pre-rRNA substrate, and we demonstrate that this interaction is required for the processing reaction in vitro. Furthermore, we show that nucleolin interacts with the U3 snoRNP. Increased levels of nucleolin, in the presence of the U3 snoRNA, activate the processing activity of a S100 cell extract. Our results suggest that the interaction of nucleolin with the pre-rRNA substrate might be a limiting step in the primary processing reaction. Nucleolin is the first identified metazoan proteinaceous factor that interacts directly with the rRNA substrate and that is required for the processing reaction. Potential roles for nucleolin in the primary processing reaction and in ribosome biogenesis are discussed.

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References

Erard M, Belenguer P, Caizergues-Ferrer M, Pantaloni A, Amalric F . A major nucleolar protein, nucleolin, induces chromatin decondensation by binding to histone H1. Eur J Biochem. 1988; 175(3):525-30. DOI: 10.1111/j.1432-1033.1988.tb14224.x. View

Beltrame M, Tollervey D . Identification and functional analysis of two U3 binding sites on yeast pre-ribosomal RNA. EMBO J. 1992; 11(4):1531-42. PMC: 556602. DOI: 10.1002/j.1460-2075.1992.tb05198.x. View

Shumard C, Eichler D . Ribosomal RNA processing. Limited cleavages of mouse preribosomal RNA by a nucleolar endoribonuclease include the early +650 processing site. J Biol Chem. 1988; 263(36):19346-52. View

Maser R, CALVET J . U3 small nuclear RNA can be psoralen-cross-linked in vivo to the 5' external transcribed spacer of pre-ribosomal-RNA. Proc Natl Acad Sci U S A. 1989; 86(17):6523-7. PMC: 297876. DOI: 10.1073/pnas.86.17.6523. View

Belenguer P, Baldin V, Mathieu C, Prats H, Bensaid M, Bouche G . Protein kinase NII and the regulation of rDNA transcription in mammalian cells. Nucleic Acids Res. 1989; 17(16):6625-36. PMC: 318355. DOI: 10.1093/nar/17.16.6625. View

Stroke I, Weiner A . The 5' end of U3 snRNA can be crosslinked in vivo to the external transcribed spacer of rat ribosomal RNA precursors. J Mol Biol. 1989; 210(3):497-512. DOI: 10.1016/0022-2836(89)90126-5. View

Peter M, Nakagawa J, Doree M, Labbe J, Nigg E . Identification of major nucleolar proteins as candidate mitotic substrates of cdc2 kinase. Cell. 1990; 60(5):791-801. DOI: 10.1016/0092-8674(90)90093-t. View

Kass S, Tyc K, Steitz J . The U3 small nucleolar ribonucleoprotein functions in the first step of preribosomal RNA processing. Cell. 1990; 60(6):897-908. DOI: 10.1016/0092-8674(90)90338-f. View

Scheer U, Benavente R . Functional and dynamic aspects of the mammalian nucleolus. Bioessays. 1990; 12(1):14-21. DOI: 10.1002/bies.950120104. View

10.

Belenguer P, Caizergues-Ferrer M, Labbe J, Doree M, Amalric F . Mitosis-specific phosphorylation of nucleolin by p34cdc2 protein kinase. Mol Cell Biol. 1990; 10(7):3607-18. PMC: 360797. DOI: 10.1128/mcb.10.7.3607-3618.1990. View

11.

Ohmori H, Murakami T, Furutani A, Higashi K, Hirano H, Gotoh S . Simultaneous activation of heat shock protein (hsp 70) and nucleolin genes during in vivo and in vitro prereplicative stages of rat hepatocytes. Exp Cell Res. 1990; 189(2):227-32. DOI: 10.1016/0014-4827(90)90240-b. View

12.

Kass S . The first pre-rRNA-processing event occurs in a large complex: analysis by gel retardation, sedimentation, and UV cross-linking. Mol Cell Biol. 1990; 10(9):4920-31. PMC: 361110. DOI: 10.1128/mcb.10.9.4920-4931.1990. View

13.

Maden B . The numerous modified nucleotides in eukaryotic ribosomal RNA. Prog Nucleic Acid Res Mol Biol. 1990; 39:241-303. DOI: 10.1016/s0079-6603(08)60629-7. View

14.

Craig N, Kass S . Sequence organization and RNA structural motifs directing the mouse primary rRNA-processing event. Mol Cell Biol. 1991; 11(1):458-67. PMC: 359650. DOI: 10.1128/mcb.11.1.458-467.1991. View

15.

Tyc K, Steitz J . A new interaction between the mouse 5' external transcribed spacer of pre-rRNA and U3 snRNA detected by psoralen crosslinking. Nucleic Acids Res. 1992; 20(20):5375-82. PMC: 334344. DOI: 10.1093/nar/20.20.5375. View

16.

Mougey E, OReilly M, Osheim Y, MILLER Jr O, Beyer A . The terminal balls characteristic of eukaryotic rRNA transcription units in chromatin spreads are rRNA processing complexes. Genes Dev. 1993; 7(8):1609-19. DOI: 10.1101/gad.7.8.1609. View

17.

Mougey E, Pape L . A U3 small nuclear ribonucleoprotein-requiring processing event in the 5' external transcribed spacer of Xenopus precursor rRNA. Mol Cell Biol. 1993; 13(10):5990-8. PMC: 364653. DOI: 10.1128/mcb.13.10.5990-5998.1993. View

18.

Lubben B, Marshallsay C, Rottmann N, Luhrmann R . Isolation of U3 snoRNP from CHO cells: a novel 55 kDa protein binds to the central part of U3 snoRNA. Nucleic Acids Res. 1993; 21(23):5377-85. PMC: 310574. DOI: 10.1093/nar/21.23.5377. View

19.

Yang T, Tsai W, Lee Y, Lei H, Lai M, Chen D . Purification and characterization of nucleolin and its identification as a transcription repressor. Mol Cell Biol. 1994; 14(9):6068-74. PMC: 359133. DOI: 10.1128/mcb.14.9.6068-6074.1994. View

20.

Eichler D, Craig N . Processing of eukaryotic ribosomal RNA. Prog Nucleic Acid Res Mol Biol. 1994; 49:197-239. DOI: 10.1016/s0079-6603(08)60051-3. View