Human eRF1 Translation Regulation

IF 1.5 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Biology Pub Date : 2024-08-07 DOI:10.1134/s0026893324700298

A. V. Shuvalov, A. A. Klishin, N. S. Biziaev, E. Y. Shuvalova, E. Z. Alkalaeva

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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.

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人类 eRF1 翻译调控

摘要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 衰减（NMD）和终止密码子的读通过程中发挥着关键作用。细胞中 eRF1 的含量会影响所有这些过程。植物和真菌已描述了通过依赖 NMD 的自律表达回路调控 eRF1 翻译的机制，但人类 eRF1 翻译的调控机制尚未研究。我们使用报告构建体研究了 eRF1 mRNA 成分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 的表达不存在依赖 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起始密码子的影响最大。根据转录起始数据库，eRF1 mRNA 的转录起始具有高度异质性，5′非翻译区的长度可变。此外，eRF1 mRNA 中 CDS 的起始密码子位于已知的短 5' 非翻译区翻译调节因子（TISU）内，该因子也会刺激转录起始异质性高的基因的 mRNA 转录。我们推测，人类 eRF1 合成的调控发生在转录和翻译两个层面。在转录水平，eRF1 5'非翻译区的长度及其上游开放阅读框的数量受到调控。这种调节反过来又在翻译水平上调节 eRF1 的生成。

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

Molecular Biology 生物-生化与分子生物学

CiteScore

1.30

自引率

8.30%

发文量

审稿时长

3 months

期刊介绍： Molecular Biology is an international peer reviewed journal that covers a wide scope of problems in molecular, cell and computational biology including genomics, proteomics, bioinformatics, molecular virology and immunology, molecular development biology, molecular evolution and related areals. Molecular Biology publishes reviews, experimental and theoretical works. Every year, the journal publishes special issues devoted to most rapidly developing branches of physical-chemical biology and to the most outstanding scientists.