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PMID:18769712

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Citation

Iwanami, N, Higuchi, T, Sasano, Y, Fujiwara, T, Hoa, VQ, Okada, M, Talukder, SR, Kunimatsu, S, Li, J, Saito, F, Bhattacharya, C, Matin, A, Sasaki, T, Shimizu, N, Mitani, H, Himmelbauer, H, Momoi, A, Kondoh, H, Furutani-Seiki, M and Takahama, Y (2008) WDR55 is a nucleolar modulator of ribosomal RNA synthesis, cell cycle progression, and teleost organ development. PLoS Genet. 4:e1000171

Abstract

The thymus is a vertebrate-specific organ where T lymphocytes are generated. Genetic programs that lead to thymus development are incompletely understood. We previously screened ethylnitrosourea-induced medaka mutants for recessive defects in thymus development. Here we report that one of those mutants is caused by a missense mutation in a gene encoding the previously uncharacterized protein WDR55 carrying the tryptophan-aspartate-repeat motif. We find that WDR55 is a novel nucleolar protein involved in the production of ribosomal RNA (rRNA). Defects in WDR55 cause aberrant accumulation of rRNA intermediates and cell cycle arrest. A mutation in WDR55 in zebrafish also leads to analogous defects in thymus development, whereas WDR55-null mice are lethal before implantation. These results indicate that WDR55 is a nuclear modulator of rRNA synthesis, cell cycle progression, and embryonic organogenesis including teleost thymus development.

Links

PubMed PMC2515640 Online version:10.1371/journal.pgen.1000171

Keywords

Amino Acid Sequence; Animals; Cell Cycle; Cell Nucleolus/genetics; Cell Nucleolus/metabolism; Fish Proteins/genetics; Fish Proteins/metabolism; Mice; Mice, Knockout; Molecular Sequence Data; Mutation, Missense; NIH 3T3 Cells; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Oryzias/genetics; Oryzias/growth & development; Oryzias/metabolism; Phenotype; RNA Processing, Post-Transcriptional; RNA, Ribosomal/biosynthesis; RNA, Ribosomal/genetics; Sequence Alignment; Thymus Gland/growth & development; Thymus Gland/metabolism; Zebrafish/genetics; Zebrafish/growth & development; Zebrafish/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

ORYLA:WDR55

involved_in

GO:0048536: spleen development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

ORYLA:WDR55

involved_in

GO:0001889: liver development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

ORYLA:WDR55

involved_in

GO:0001654: eye development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

ORYLA:WDR55

involved_in

GO:0006364: rRNA processing

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

ORYLA:WDR55

located_in

GO:0005730: nucleolus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

ORYLA:WDR55

involved_in

GO:0048538: thymus development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

ORYLA:WDR55

involved_in

GO:0060465: pharynx development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

ORYLA:WDR55

involved_in

GO:0060322: head development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:WDR55

involved_in

GO:0001654: eye development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:WDR55

involved_in

GO:0048794: swim bladder development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:WDR55

involved_in

GO:0048538: thymus development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:WDR55

involved_in

GO:0060465: pharynx development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DANRE:WDR55

involved_in

GO:0048538: thymus development

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-GENO-080910-2

P

Seeded From UniProt

complete

MOUSE:WDR55

located_in

GO:0005737: cytoplasm

ECO:0000315: mutant phenotype evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:WDR55

involved_in

GO:0006364: rRNA processing

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:WDR55

located_in

GO:0005730: nucleolus

ECO:0000315: mutant phenotype evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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