LARP1 on TOP of ribosome production.
LARP1 on TOP of ribosome production.
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DOI：
10.1002/wrna.1480
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发表时间：
2018-09
期刊：
影响因子：
--
通讯作者：
Berman AJ
中科院分区：
文献类型：
--
作者：
Fonseca BD;Lahr RM;Damgaard CK;Alain T;Berman AJ
核糖体是所有生物体的基本单位，它指挥蛋白质合成，最终促进细胞生长（细胞质量的积累）和细胞增殖（细胞数量的增加）。真核核糖体由4种核糖体rna和多达80种核糖体蛋白（RPs）组成。尽管核糖体在每一个生物体中都起着基本的作用，但我们目前对高等真核生物如何产生各种核糖体成分的理解是不完整的。揭示人类细胞产生功能性核糖体的机制可能对人类疾病产生深远的影响。近年来的生物化学和结构研究表明，la相关蛋白1 （LARP1）在核糖体蛋白的产生中起着重要的作用。LARP1是一种rna结合蛋白，属于LARP超家族；它控制编码核糖体蛋白和翻译因子的mrna的翻译和稳定性，这些mrna以5 ‘端寡聚嘧啶（5 ’ TOP）基序为特征，因此被称为TOP mrna。LARP1的活性受哺乳动物雷帕霉素靶蛋白复合物1 （mTORC1）的调控：雷帕霉素靶蛋白是一种真核蛋白激酶复合物，整合了营养感知和mRNA翻译，特别是TOP mRNA的翻译。在这篇综述中，我们综述了LARP1在多细胞真核生物中控制核糖体产生的作用。核糖体的产生对细胞来说是相当大的能量投入——RNAs和核糖体蛋白是最丰富的一类rna和蛋白质——因此，它们的产生必须在时间上和化学计量上同步，以确保核糖体的有效组装。多细胞真核生物在mRNA翻译水平上控制核糖体蛋白的产生。la相关蛋白1 （LARP1）是哺乳动物雷帕霉素靶蛋白复合物1 （mTORC1）的新靶点，也是核糖体蛋白mRNA翻译的关键抑制因子。LARP1结合编码核糖体蛋白和翻译因子的mrna的7-甲基鸟苷三磷酸（m7Gppp）帽和邻近的5 ‘端寡聚嘧啶（5’TOP）基序。在此过程中，LARP1阻止真核起始因子4E （eIF4E）与m7Gppp帽的结合，并阻断eIF4F复合物的组装以及随后40S核糖体亚基对核糖体蛋白mrna的募集。mTORC1通过调节LARP1与m7Gppp帽和TOP mRNA的特征邻近5'TOP基序的磷酸化和关联来控制TOP mRNA的翻译。
The ribosome is an essential unit of all living organisms that commands protein synthesis, ultimately fuelling cell growth (accumulation of cell mass) and cell proliferation (increase in cell number). The eukaryotic ribosome consists of four ribosomal RNAs and up to 80 ribosomal proteins (RPs). Despite its fundamental role in every living organism, our present understanding of how higher eukaryotes produce the various ribosome components is incomplete. Uncovering the mechanisms utilized by human cells to generate functional ribosomes will likely have far-reaching implications in human disease. Recent biochemical and structural studies revealed La-related protein 1 (LARP1) as a key new player in ribosomal protein production. LARP1 is an RNA-binding protein that belongs to the LARP superfamily; it controls the translation and stability of the mRNAs that encode ribosomal proteins and translation factors, which are characterized by a 5′ terminal oligopyrimidine (5′TOP) motif and are thus known as TOP mRNAs. The activity of LARP1 is regulated by the mammalian target of rapamycin complex 1 (mTORC1): an eukaryotic protein kinase complex that integrates nutrient sensing with mRNA translation, particularly that of TOP mRNAs. In this review, we provide an overview of the role of LARP1 in the control of ribosome production in multicellular eukaryotes. Ribosome production is a considerable energy investment for the cell—rRNAs and ribosomal proteins are amongst the most abundant classes of RNAs and proteins—and their production must, therefore, be synchronized temporally and stoichiometrically to ensure efficient ribosome assembly. Multicellular eukaryotes control ribosomal protein production at the level of mRNA translation. La-related protein 1 (LARP1) is a novel target of mammalian target of rapamycin complex 1 (mTORC1) and key repressor of ribosomal protein mRNA translation. LARP1 binds the 7-methyl guanosine triphosphate (m7Gppp) cap and adjacent 5′terminal oligopyrimidine (5′TOP) motif of mRNAs encoding ribosomal proteins and translation factors. In doing so, LARP1 prevents binding of the eukaryotic initiation factor 4E (eIF4E) to the m7Gppp cap and blocks the assembly of the eIF4F complex and the subsequent recruitment of the 40S ribosomal subunit to ribosomal proteins mRNAs. mTORC1 controls TOP mRNA translation by regulating the phosphorylation and association of LARP1 with the m7Gppp cap and the characteristic adjacent 5′TOP motif of TOP mRNAs.
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DOI：
10.2183/pjab.91.394
发表时间：
2015
期刊：
Proceedings of the Japan Academy. Series B, Physical and biological sciences
影响因子：
--
作者：
Furuichi Y
通讯作者：
Furuichi Y
影响因子：
4.8
作者：
Fonseca, Bruno D.;Smith, Ewan M.;Proud, Christopher G.
通讯作者：
Proud, Christopher G.
影响因子：
3.5
作者：
Biberman, Y;Meyuhas, O
通讯作者：
Meyuhas, O
影响因子：
10.5
作者：
Damgaard, Christian Kroun;Lykke-Andersen, Jens
通讯作者：
Lykke-Andersen, Jens
DOI：
10.1016/j.bbagrm.2010.01.011
发表时间：
2010-05
影响因子：
4.7
作者：
Bayfield, Mark A.;Yang, Ruiqing;Maraia, Richard J.
通讯作者：
Maraia, Richard J.