Lso2 is a conserved ribosome-bound protein required for translational recovery in yeast.
Lso2 is a conserved ribosome-bound protein required for translational recovery in yeast.
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DOI：
10.1371/journal.pbio.2005903
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发表时间：
2018-09
期刊：
影响因子：
9.8
通讯作者：
Gilbert WV
中科院分区：
文献类型：
--
作者：
Wang YJ;Vaidyanathan PP;Rojas-Duran MF;Udeshi ND;Bartoli KM;Carr SA;Gilbert WV
核糖体结合蛋白在蛋白质合成、基因调控和细胞内环境稳定中发挥广泛的作用，但功能性核糖体结合蛋白的完整补充仍然未知。使用定量质谱，我们确定了后期注释的短开放阅读框架2（LSO 2）作为核糖体相关蛋白，在真核生物中广泛保守。Lso 2及其人类直系同源卷曲螺旋结构域包含124（CCDC 124）的全基因组交联和免疫沉淀在A位点附近的区域中回收了25 S核糖体RNA，该区域与GTdR激活中心重叠。与此位置一致，Lso 2也与大多数tRNA交联。缺乏LSO 2（lso 2 Δ）的酵母的核糖体分析显示，在从稳定期恢复期间，大多数基因的翻译减少了4倍以上。核糖体在起始密码子处积累，从终止密码子处耗尽，并且在Iso 2 Δ中显示密码子特异性占据变化。这些缺陷，以及Lso 2/CCDC 124的特异性核糖体结合活性的保守性，表明在翻译和生理学中具有广泛的重要功能。翻译，或从信使RNA（mRNA）产生蛋白质，是由一个普遍保守的大分子机器，称为核糖体催化的。核糖体结合因子也是翻译的所有子步骤所必需的，从mRNA的初始募集到肽链延伸到成熟多肽的释放。然而，许多核糖体相互作用已被确定，其对翻译和生理的影响是未知的。在这里，我们表明，未表征的酵母蛋白后期注释的短开放阅读框2（LSO 2）交联的核糖体的一个区域，该区域是通过翻译的所有子步骤的准确进展的基础，GTdR激活中心。这种特异性结合活性在Lso 2的人类直系同源物中是保守的，卷曲螺旋结构域包含124（CCDC 124）。Iso 2的突变体在从长期饥饿中恢复的过程中也表现出严重的翻译缺陷，包括未能在大多数mRNA上启动和对肽链延伸的一般阻断。我们建议，这些缺陷可能会出现从LSO 2在调节的活性或完整性的核糖体GTdR激活中心在具有挑战性的增长制度的功能。
Ribosome-binding proteins function broadly in protein synthesis, gene regulation, and cellular homeostasis, but the complete complement of functional ribosome-bound proteins remains unknown. Using quantitative mass spectrometry, we identified late-annotated short open reading frame 2 (Lso2) as a ribosome-associated protein that is broadly conserved in eukaryotes. Genome-wide crosslinking and immunoprecipitation of Lso2 and its human ortholog coiled-coil domain containing 124 (CCDC124) recovered 25S ribosomal RNA in a region near the A site that overlaps the GTPase activation center. Consistent with this location, Lso2 also crosslinked to most tRNAs. Ribosome profiling of yeast lacking LSO2 (lso2Δ) revealed global translation defects during recovery from stationary phase with translation of most genes reduced more than 4-fold. Ribosomes accumulated at start codons, were depleted from stop codons, and showed codon-specific changes in occupancy in lso2Δ. These defects, and the conservation of the specific ribosome-binding activity of Lso2/CCDC124, indicate broadly important functions in translation and physiology. Translation, or the production of protein from messenger RNA (mRNA), is catalyzed by a universally conserved macromolecular machine known as the ribosome. Ribosome-binding factors are also required for all substeps of translation, from initial recruitment of mRNA to peptide chain elongation to release of the mature polypeptide. However, many ribosome interactors have been identified whose effects on translation and physiology are unknown. Here, we show that the uncharacterized yeast protein late-annotated short open reading frame 2 (Lso2) crosslinks to a region of the ribosome that underlies accurate progression through all substeps of translation, the GTPase activation center. This specific binding activity is conserved in the human ortholog of Lso2, coiled-coil domain containing 124 (CCDC124). Null mutants of lso2 also show severe translation defects during recovery from extended starvation, including failure to initiate on most mRNAs and a general block to peptide chain elongation. We propose that these defects could arise from a function for Lso2 in modulating the activity or integrity of the ribosome GTPase activation center during challenging growth regimes.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
严格控制核糖体依赖性激活。
影响因子：
64.8
作者：
Brown A;Fernández IS;Gordiyenko Y;Ramakrishnan V
通讯作者：
Ramakrishnan V
影响因子：
8.8
作者：
Conway AE;Van Nostrand EL;Pratt GA;Aigner S;Wilbert ML;Sundararaman B;Freese P;Lambert NJ;Sathe S;Liang TY;Essex A;Landais S;Burge CB;Jones DL;Yeo GW
通讯作者：
Yeo GW
DOI：
10.1073/pnas.96.22.12345
发表时间：
1999-10-26
影响因子：
11.1
作者：
Agafonov, DE;Kolb, VA;Spirin, AS
通讯作者：
Spirin, AS
影响因子：
16.6
作者：
Beckmann BM;Horos R;Fischer B;Castello A;Eichelbaum K;Alleaume AM;Schwarzl T;Curk T;Foehr S;Huber W;Krijgsveld J;Hentze MW
通讯作者：
Hentze MW