Nom1 mediates pancreas development by regulating ribosome biogenesis in zebrafish.
Nom1 mediates pancreas development by regulating ribosome biogenesis in zebrafish.
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DOI：
10.1371/journal.pone.0100796
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Lin S
中科院分区：
文献类型：
--
作者：
Qin W;Chen Z;Zhang Y;Yan R;Yan G;Li S;Zhong H;Lin S
核糖体生物合成是细胞正常功能和发育的重要生物学过程。导致核糖体生物合成不当的缺陷可导致疾病，如Diamond-Blackfan贫血和Shwachman-Bodian-Diamond综合征。核仁蛋白是蛋白质的一个大家族，并且参与许多细胞过程，包括核糖体生物合成的调节。通过正向遗传筛选和定位克隆，我们确定并表征了一个斑马鱼行携带突变的核仁蛋白与MIF 4G结构域1（nom 1），它编码一个保守的nucceolar蛋白与pre-rRNA加工的作用。斑马鱼nom 1突变体在内胚层发育，特别是外分泌胰腺中表现出重大缺陷。进一步的研究表明，ptf 1a表达的胰腺祖细胞的增殖受损主要促成了表型。RNA-seq和分子生物学分析表明，核糖体生物合成和前体mRNA剪接都受到影响，在突变体胚胎。核糖体组装的几种缺陷已被证明具有p53依赖性机制。在nom 1突变体中，p53的丢失并不能挽救胰腺缺陷，这表明p53的独立作用。进一步的研究表明，蛋白磷酸酶1 α，一个相互作用的蛋白质Nom 1，可以部分拯救胰腺的缺陷，在nom 1 morphants，如果人的核仁定位信号序列被人为添加。这表明Nom 1靶向Pp 1 α进入核仁对胰腺增殖是重要的。总之，我们的研究揭示了一个新的机制，涉及Nom 1在控制脊椎动物外分泌胰腺的形成。
Ribosome biogenesis is an important biological process for proper cellular function and development. Defects leading to improper ribosome biogenesis can cause diseases such as Diamond-Blackfan anemia and Shwachman-Bodian-Diamond syndrome. Nucleolar proteins are a large family of proteins and are involved in many cellular processes, including the regulation of ribosome biogenesis. Through a forward genetic screen and positional cloning, we identified and characterized a zebrafish line carrying mutation in nucleolar protein with MIF4G domain 1 (nom1), which encodes a conserved nulceolar protein with a role in pre-rRNA processing. Zebrafish nom1 mutants exhibit major defects in endoderm development, especially in exocrine pancreas. Further studies revealed that impaired proliferation of ptf1a-expressing pancreatic progenitor cells mainly contributed to the phenotype. RNA-seq and molecular analysis showed that ribosome biogenesis and pre-mRNA splicing were both affected in the mutant embryos. Several defects of ribosome assembly have been shown to have a p53-dependent mechanism. In the nom1 mutant, loss of p53 did not rescue the pancreatic defect, suggesting a p53-independent role. Further studies indicate that protein phosphatase 1 alpha, an interacting protein to Nom1, could partially rescue the pancreatic defect in nom1 morphants if a human nucleolar localization signal sequence was artificially added. This suggests that targeting Pp1α into the nucleolus by Nom1 is important for pancreatic proliferation. Altogether, our studies revealed a new mechanism involving Nom1 in controlling vertebrate exocrine pancreas formation.
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影响因子：
3.7
作者：
Hozumi S;Hirabayashi R;Yoshizawa A;Ogata M;Ishitani T;Tsutsumi M;Kuroiwa A;Itoh M;Kikuchi Y
通讯作者：
Kikuchi Y
影响因子：
4.4
作者：
通讯作者：
--
DOI：
10.1073/pnas.95.12.6887
发表时间：
1998-06-09
影响因子：
11.1
作者：
Marciniak, RA;Lombard, DB;Guarente, L
通讯作者：
Guarente, L
影响因子：
3.5
作者：
Heiss, NS;Girod, A;Poustka, A
通讯作者：
Poustka, A
影响因子：
4.8
作者：
Gunawardena, Shanaka R.;Ruis, Brian L.;Conklin, Kathleen F.
通讯作者：
Conklin, Kathleen F.