40S ribosomal subunits scan mRNA for the start codon by one-dimensional diffusion.

IF 5 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
RNA Pub Date : 2025-09-16 DOI:10.1261/rna.080493.125
Hironao Wakabayashi, Mingyi Zhu, Elizabeth J Grayhack, David H Mathews, Dmitri N Ermolenko
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引用次数: 0

Abstract

During eukaryotic translation initiation, the small (40S) ribosomal subunit is recruited to the 5' cap and subsequently scans the 5' untranslated region (5' UTR) of mRNA in search of the start codon. The molecular mechanism of mRNA scanning remains unclear, particularly the requirement for and identity of a translocase. Here, using GFP reporters in Saccharomyces cerevisiae, we show that order-of-magnitude variations in the length of unstructured 5' UTRs have only modest effects on protein synthesis, whereas structured 5' UTRs strongly inhibit translation. Thus, when not hindered by secondary structure, mRNA scanning is not rate limiting. Loss-of-function mutations in eIF4A, Ded1, and Slh1 reveal that these translational helicases are dispensable for mRNA scanning. Our data suggest that one-dimensional diffusion predominately enables 40S movement along the 5' UTR during mRNA scanning.

40S核糖体亚基通过一维扩散扫描mRNA寻找起始密码子。
在真核生物翻译起始过程中,小(40S)核糖体亚基被招募到5‘帽上,随后扫描mRNA的5’非翻译区(5' UTR)以寻找起始密码子。mRNA扫描的分子机制尚不清楚,特别是对转位酶的要求和身份。在这里,我们利用酿酒酵母的GFP报告基因,发现非结构化5' utr长度的数量级变化对蛋白质合成只有适度的影响,而结构化5' utr强烈抑制翻译。因此,当不受二级结构阻碍时,mRNA扫描不受速率限制。eIF4A、Ded1和Slh1的功能缺失突变表明,这些翻译解旋酶在mRNA扫描中是必不可少的。我们的数据表明,在mRNA扫描期间,一维扩散主要使40S沿着5' UTR移动。
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
RNA
RNA 生物-生化与分子生物学
CiteScore
8.30
自引率
2.20%
发文量
101
审稿时长
2.6 months
期刊介绍: RNA is a monthly journal which provides rapid publication of significant original research in all areas of RNA structure and function in eukaryotic, prokaryotic, and viral systems. It covers a broad range of subjects in RNA research, including: structural analysis by biochemical or biophysical means; mRNA structure, function and biogenesis; alternative processing: cis-acting elements and trans-acting factors; ribosome structure and function; translational control; RNA catalysis; tRNA structure, function, biogenesis and identity; RNA editing; rRNA structure, function and biogenesis; RNA transport and localization; regulatory RNAs; large and small RNP structure, function and biogenesis; viral RNA metabolism; RNA stability and turnover; in vitro evolution; and RNA chemistry.
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