[Human eRF1 Translation Regulation].

Q3 Medicine
A V Shuvalov, A A Klishin, N S Biziaev, E Y Shuvalova, E Z Alkalaeva
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引用次数: 0

Abstract

Eukaryotic translation release factor eRF1 is an important cellular protein that plays a key role in translation termination, nonsense-mediated mRNA decay (NMD), and readthrough of stop codons. The amount of eRF1 in the cell influences all these processes. The mechanism of regulation of eRF1 translation through an autoregulatory NMD-dependent expression circuit has been described for plants and fungi, but the mechanisms of regulation of human eRF1 translation have not yet been studied. Using reporter constructs, we studied the effect of eRF1 mRNA elements on its translation in cell-free translation systems and HEK293 cell culture. Our data indicate the absence of an NMD-dependent autoregulatory circuit for human eRF1 expression. We found that the translation of the eRF1 coding sequence is most strongly influenced by the 5' untranslated region of eRF1 mRNA and the start codon of the upstream open reading frame. According to the transcription start database, eRF1 mRNA is characterized by high heterogeneity of the transcription start and a variable 5' untranslated region in length. In addition, the start codon of the CDS in eRF1 mRNA is located within the known translational regulator of short 5' untranslated regions (TISU), which also stimulates mRNA transcription of genes with high transcription start heterogeneity. We hypothesize that regulation of human eRF1 synthesis occurs at both the transcriptional and translational levels. At the transcription level, the length of the eRF1 5' untranslated region and the number of the upstream open reading frames in it are regulated. This regulation in turn, regulates the production of eRF1 at the translation level.

[人类eRF1翻译规则]。
真核生物翻译释放因子eRF1是一种重要的细胞蛋白,在翻译终止、无义介导的mRNA衰变(NMD)和终止密码子的读取中起关键作用。细胞中eRF1的数量影响所有这些过程。植物和真菌通过nmd依赖的自调节表达回路调控eRF1翻译的机制已被描述,但人类eRF1翻译的调控机制尚未被研究。通过构建报告因子,我们研究了eRF1 mRNA元件在无细胞翻译系统和HEK293细胞培养中对其翻译的影响。我们的数据表明,人类eRF1表达缺乏依赖nmd的自动调节回路。我们发现eRF1编码序列的翻译受eRF1 mRNA的5'非翻译区和上游开放阅读框的起始密码子的影响最大。根据转录起始数据库,eRF1 mRNA具有转录起始高度异质性和长度可变的5'非翻译区。此外,eRF1 mRNA中CDS的起始密码子位于已知的短5'非翻译区(TISU)的翻译调控因子中,这也刺激了转录起始异质性高的基因的mRNA转录。我们假设人类eRF1合成的调控发生在转录和翻译水平上。在转录水平上,eRF1 5'非翻译区的长度和上游开放阅读框的数量受到调控。这种调控反过来又在翻译水平上调控eRF1的产生。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Molekulyarnaya Biologiya
Molekulyarnaya Biologiya Medicine-Medicine (all)
CiteScore
0.70
自引率
0.00%
发文量
131
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