WDR55 is a nucleolar modulator of ribosomal RNA synthesis, cell cycle progression, and teleost organ development.
WDR55 is a nucleolar modulator of ribosomal RNA synthesis, cell cycle progression, and teleost organ development.
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DOI：
10.1371/journal.pgen.1000171
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发表时间：
2008-08-29
期刊：
影响因子：
4.5
通讯作者：
Takahama Y
中科院分区：
文献类型：
--
作者：
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;Takahama Y
胸腺是脊椎动物特有的器官，在那里产生T淋巴细胞。导致胸腺发育的遗传程序还不完全清楚。我们以前筛选乙基亚硝基脲诱导青鳉突变体的胸腺发育的隐性缺陷。在这里，我们报告说，这些突变体之一是由错义突变的基因编码以前未知的蛋白质WDR 55携带的Dahan-天冬氨酸重复基序。我们发现WDR 55是一种新的参与核糖体RNA（rRNA）产生的核仁蛋白。WDR 55的缺陷导致rRNA中间体的异常积累和细胞周期停滞。斑马鱼中WDR 55的突变也导致胸腺发育的类似缺陷，而WDR 55缺失小鼠在植入前是致命的。这些结果表明WDR 55是rRNA合成、细胞周期进程和胚胎器官发生（包括硬骨鱼胸腺发育）的核调节剂。青鳉（Oryzias latipes）是一种小型淡水鱼，可用于正向和反向遗传学研究。各种近交系的可用性是青鳉相对于斑马鱼的明显优势，特别是在免疫系统的研究中。胸腺是脊椎动物特有的主要免疫器官，支持T淋巴细胞的产生。胸腺发育缺陷往往会导致T淋巴细胞发育异常，导致免疫缺陷或自身免疫。然而，胸腺发育的分子途径尚未完全揭示。在这里，我们报告的胸腺缺陷青鳉突变体之一负责基因的定位克隆。我们发现，hkc表型是由编码以前未表征的蛋白质WDR 55的基因中的错义突变引起的。我们的研究结果表明，WDR 55是一种新的核仁调节剂的rRNA生物合成，细胞周期的进展，脊椎动物的器官，包括硬骨鱼胸腺的发展。这些结果不仅提供了一种新的rRNA产生机制存在的证据，而且还表明，WDR 55的功能障碍导致细胞周期停滞和发育失败，包括胸腺发育缺陷。
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. Medaka, Oryzias latipes, is a small freshwater fish that is useful for studies of forward and reverse genetics. The availability of various inbred strains is the distinct advantage of medaka over zebrafish, especially in studies of the immune system. The thymus is a primary immune organ that is unique to vertebrates and supports the generation of T lymphocytes. Defective thymus development tends to cause abnormal T lymphocyte development, resulting in immunodeficiency or autoimmunity. However, the molecular pathways underlying thymus development have not been fully uncovered. Here we report the positional cloning of a gene responsible for one of the thymus-defective medaka mutants. We find that the hkc phenotype is caused by a missense mutation in a gene encoding the previously uncharacterized protein WDR55. Our results indicate that WDR55 is a novel nucleolar modulator of rRNA biosynthesis, cell cycle progression, and vertebrate development of organs, including teleost thymus. These results not only provide evidence of the existence of a new mechanism of rRNA production but also demonstrate that the malfunction of WDR55 causes cell cycle arrest and developmental failure, including defective thymus development.
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rRNA 加工和 60S 核糖体亚基的核内运输需要必需的 WD 重复蛋白 Rsa4p。
影响因子：
14.9
作者：
de la Cruz J;Sanz-Martínez E;Remacha M
通讯作者：
Remacha M
DOI：
10.1083/jcb.200501141
发表时间：
2005-08-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hölzel M;Rohrmoser M;Schlee M;Grimm T;Harasim T;Malamoussi A;Gruber-Eber A;Kremmer E;Hiddemann W;Bornkamm GW;Eick D
通讯作者：
Eick D
影响因子：
10.5
作者：
Allende, ML;Amsterdam, A;Hopkins, N
通讯作者：
Hopkins, N
影响因子：
2.6
作者：
Khorasani, MZ;Hennig, S;Himmelbauer, H
通讯作者：
Himmelbauer, H
影响因子：
1.9
作者：
Adriani, M;Martinez-Mir, A;Pignata, C
通讯作者：
Pignata, C