Variants of the 5'-terminal region of p53 mRNA influence the ribosomal scanning and translation efficiency.
Variants of the 5'-terminal region of p53 mRNA influence the ribosomal scanning and translation efficiency.
复制标题
p53 mRNA的5'-末端区域的变体影响核糖体扫描和翻译效率。
DOI：
10.1038/s41598-018-20010-2
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发表时间：
2018-01-24
影响因子：
4.6
通讯作者：
Ciesiołka J
中科院分区：
文献类型：
--
作者：
Zydowicz-Machtel P;Swiatkowska A;Popenda Ł;Gorska A;Ciesiołka J
p53蛋白是主要的细胞周期调节因子之一。所述蛋白质表达为至少十二种蛋白质同种型，所述蛋白质同种型由使用选择性启动子、选择性剪接或下游起始密码子产生。重要的是，越来越多的证据表明，p53 mRNA的翻译起始可能受到p53 mRNA转录本5′-末端区域的天然变体的结构和长度的调节。在此，合成了几种具有可变长度的p53 5′-末端区域和编码荧光素酶报告蛋白的mRNA构建体，并在兔网织红细胞裂解物系统中原位连续监测其翻译。此外，制备了四种另外的mRNA构建体。在两个构建体中，AUG 1起始密码子的结构背景被改变，而在另两个构建体中，存在于p53 5′-末端区域的特征性发夹基序被改变。最后两个构建体的翻译也在帽类似物的存在下进行，以测试5′-末端区域在帽非依赖性翻译起始中的功能。与5′端长度、二级结构稳定元件、起始密码子的结构环境和IRES元件有关的几个结构因子的叠加对核糖体扫描和翻译效率有很大影响。
The p53 protein is one of the major cell cycle regulators. The protein is expressed as at least twelve protein isoforms resulting from the use of alternative promoters, alternative splicing or downstream initiation codons. Importantly, there is growing evidence that translation initiation of p53 mRNA may be regulated by the structure and length of the naturally occurring variants of the 5′-terminal region of p53 mRNA transcripts. Here, several mRNA constructs were synthesized with variable length of the p53 5′-terminal regions and encoding luciferase reporter protein, and their translation was monitored continuously in situ in a rabbit reticulocyte lysate system. Moreover, four additional mRNA constructs were prepared. In two constructs, the structural context of AUG1 initiation codon was altered while in the other two constructs, characteristic hairpin motifs present in the p53 5′-terminal region were changed. Translation of the last two constructs was also performed in the presence of the cap analogue to test the function of the 5′-terminal region in cap-independent translation initiation. Superposition of several structural factors connected with the length of the 5′-terminal region, stable elements of the secondary structure, structural environment of the initiation codon and IRES elements greatly influenced the ribosomal scanning and translation efficiency.
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DOI：
10.4161/trla.28387
发表时间：
2014
期刊：
Translation (Austin, Tex.)
影响因子：
--
作者：
Asano K
通讯作者：
Asano K
影响因子：
5.6
作者：
Ciesiolka, J;Michalowski, D;Krzyzosiak, WJ
通讯作者：
Krzyzosiak, WJ
影响因子：
4.5
作者：
Babendure, JR;Babendure, JL;Tsien, RY
通讯作者：
Tsien, RY
影响因子：
8
作者：
Candeias, M. M.;Powell, D. J.;Fahraeus, R.
通讯作者：
Fahraeus, R.
影响因子：
3.6
作者：
Berthelot, K;Muldoon, M;McCarthy, JEG
通讯作者：
McCarthy, JEG