Las1L is a Nucleolar Protein Required for Cell Proliferation and Ribosome Biogenesis

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2010 Jul 22

PMID 20647540

Citations 42

Authors

Christopher D Castle

Erica K Cassimere

Jinho Lee

Catherine Denicourt

Affiliations

Soon will be listed here.

Abstract

Ribosome biogenesis is a highly regulated process ensuring that cell growth (increase in biomass) is coordinated with cell proliferation. The formation of eukaryotic ribosomes is a multistep process initiated by the transcription and processing of rRNA in the nucleolus. Concomitant with this, several preribosomal particles, which transiently associate with numerous nonribosomal factors before mature 60S and 40S subunits are formed and exported in the cytoplasm, are generated. Here we identify Las1L as a previously uncharacterized nucleolar protein required for ribosome biogenesis. Depletion of Las1L causes inhibition of cell proliferation characterized by a G1 arrest dependent on the tumor suppressor p53. Moreover, we demonstrate that Las1L is crucial for ribosome biogenesis and that depletion of Las1L leads to inhibition of rRNA processing and failure to synthesize the mature 28S rRNA. Taken together, our data demonstrate that Las1L is essential for cell proliferation and biogenesis of the 60S ribosomal subunit.

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References

Gomez-Roman N, Grandori C, Eisenman R, White R . Direct activation of RNA polymerase III transcription by c-Myc. Nature. 2003; 421(6920):290-4. DOI: 10.1038/nature01327. View

Doseff A, Arndt K . LAS1 is an essential nuclear protein involved in cell morphogenesis and cell surface growth. Genetics. 1995; 141(3):857-71. PMC: 1206850. DOI: 10.1093/genetics/141.3.857. View

Boisvert F, van Koningsbruggen S, Navascues J, Lamond A . The multifunctional nucleolus. Nat Rev Mol Cell Biol. 2007; 8(7):574-85. DOI: 10.1038/nrm2184. View

Wang W, Budhu A, Forgues M, Wang X . Temporal and spatial control of nucleophosmin by the Ran-Crm1 complex in centrosome duplication. Nat Cell Biol. 2005; 7(8):823-30. DOI: 10.1038/ncb1282. View

Pestov D, Lapik Y, Lau L . Assays for ribosomal RNA processing and ribosome assembly. Curr Protoc Cell Biol. 2008; Chapter 22:Unit 22.11. DOI: 10.1002/0471143030.cb2211s39. View

Maggi Jr L, Kuchenruether M, Dadey D, Schwope R, Grisendi S, Townsend R . Nucleophosmin serves as a rate-limiting nuclear export chaperone for the Mammalian ribosome. Mol Cell Biol. 2008; 28(23):7050-65. PMC: 2593371. DOI: 10.1128/MCB.01548-07. View

Oeffinger M, Tollervey D . Yeast Nop15p is an RNA-binding protein required for pre-rRNA processing and cytokinesis. EMBO J. 2003; 22(24):6573-83. PMC: 291811. DOI: 10.1093/emboj/cdg616. View

Dez C, Tollervey D . Ribosome synthesis meets the cell cycle. Curr Opin Microbiol. 2004; 7(6):631-7. DOI: 10.1016/j.mib.2004.10.007. View

Zhang C, Comai L, Johnson D . PTEN represses RNA Polymerase I transcription by disrupting the SL1 complex. Mol Cell Biol. 2005; 25(16):6899-911. PMC: 1190253. DOI: 10.1128/MCB.25.16.6899-6911.2005. View

10.

Sirri V, Urcuqui-Inchima S, Roussel P, Hernandez-Verdun D . Nucleolus: the fascinating nuclear body. Histochem Cell Biol. 2007; 129(1):13-31. PMC: 2137947. DOI: 10.1007/s00418-007-0359-6. View

11.

van Riggelen J, Yetil A, Felsher D . MYC as a regulator of ribosome biogenesis and protein synthesis. Nat Rev Cancer. 2010; 10(4):301-9. DOI: 10.1038/nrc2819. View

12.

Tschochner H, Hurt E . Pre-ribosomes on the road from the nucleolus to the cytoplasm. Trends Cell Biol. 2003; 13(5):255-63. DOI: 10.1016/s0962-8924(03)00054-0. View

13.

Fingerman I, Nagaraj V, Norris D, Vershon A . Sfp1 plays a key role in yeast ribosome biogenesis. Eukaryot Cell. 2003; 2(5):1061-8. PMC: 219361. DOI: 10.1128/EC.2.5.1061-1068.2003. View

14.

Galani K, Nissan T, Petfalski E, Tollervey D, Hurt E . Rea1, a dynein-related nuclear AAA-ATPase, is involved in late rRNA processing and nuclear export of 60 S subunits. J Biol Chem. 2004; 279(53):55411-8. DOI: 10.1074/jbc.M406876200. View

15.

Yuan X, Zhou Y, Casanova E, Chai M, Kiss E, Grone H . Genetic inactivation of the transcription factor TIF-IA leads to nucleolar disruption, cell cycle arrest, and p53-mediated apoptosis. Mol Cell. 2005; 19(1):77-87. DOI: 10.1016/j.molcel.2005.05.023. View

16.

Thomson E, Tollervey D . Nop53p is required for late 60S ribosome subunit maturation and nuclear export in yeast. RNA. 2005; 11(8):1215-24. PMC: 1370805. DOI: 10.1261/rna.2720205. View

17.

Rohrmoser M, Holzel M, Grimm T, Malamoussi A, Harasim T, Orban M . Interdependence of Pes1, Bop1, and WDR12 controls nucleolar localization and assembly of the PeBoW complex required for maturation of the 60S ribosomal subunit. Mol Cell Biol. 2007; 27(10):3682-94. PMC: 1899993. DOI: 10.1128/MCB.00172-07. View

18.

Kressler D, Hurt E, Bassler J . Driving ribosome assembly. Biochim Biophys Acta. 2009; 1803(6):673-83. DOI: 10.1016/j.bbamcr.2009.10.009. View

19.

Budde A, Grummt I . p53 represses ribosomal gene transcription. Oncogene. 1999; 18(4):1119-24. DOI: 10.1038/sj.onc.1202402. View

20.

Pestov D, Strezoska Z, Lau L . Evidence of p53-dependent cross-talk between ribosome biogenesis and the cell cycle: effects of nucleolar protein Bop1 on G(1)/S transition. Mol Cell Biol. 2001; 21(13):4246-55. PMC: 87085. DOI: 10.1128/MCB.21.13.4246-4255.2001. View