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多聚（A）尾长度与翻译效率之间偶联的分子基础。

The molecular basis of coupling between poly(A)-tail length and translational efficiency.

机构信息

Howard Hughes Medical Institute, Cambridge, United States.

Whitehead Institute for Biomedical Research, Cambridge, United States.

出版信息

Elife. 2021 Jul 2;10:e66493. doi: 10.7554/eLife.66493.

DOI:10.7554/eLife.66493
PMID:34213414
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8253595/
Abstract

In animal oocytes and early embryos, mRNA poly(A)-tail length strongly influences translational efficiency (TE), but later in development this coupling between tail length and TE disappears. Here, we elucidate how this coupling is first established and why it disappears. Overexpressing cytoplasmic poly(A)-binding protein (PABPC) in oocytes specifically improved translation of short-tailed mRNAs, thereby diminishing coupling between tail length and TE. Thus, strong coupling requires limiting PABPC, implying that in coupled systems longer-tail mRNAs better compete for limiting PABPC. In addition to expressing excess PABPC, post-embryonic mammalian cell lines had two other properties that prevented strong coupling: terminal-uridylation-dependent destabilization of mRNAs lacking bound PABPC, and a regulatory regime wherein PABPC contributes minimally to TE. Thus, these results revealed three fundamental mechanistic requirements for coupling and defined the context-dependent functions for PABPC, which promotes TE but not mRNA stability in coupled systems and mRNA stability but not TE in uncoupled systems.

摘要

在动物卵母细胞和早期胚胎中，mRNA 多聚（A）尾长强烈影响翻译效率（TE），但在发育后期，这种尾长与 TE 的耦合消失了。在这里，我们阐明了这种耦合是如何首先建立的，以及为什么它会消失。在卵母细胞中特异性过表达细胞质多聚（A）结合蛋白（PABPC）特别改善了短尾 mRNA 的翻译，从而降低了尾长与 TE 之间的耦合。因此，强耦合需要限制 PABPC，这意味着在耦合系统中，长尾 mRNA 更好地竞争有限的 PABPC。除了表达过量的 PABPC 外，后生哺乳动物细胞系还有另外两个特性，阻止了强耦合：缺乏结合 PABPC 的 mRNA 的末端尿嘧啶依赖性不稳定性，以及 PABPC 贡献最小的调节机制到 TE。因此，这些结果揭示了耦合的三个基本机制要求，并定义了 PABPC 的上下文相关功能，它在耦合系统中促进 TE，但不促进 mRNA 稳定性，在非耦合系统中促进 mRNA 稳定性，但不促进 TE。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a10b/8253595/26378a7db6ee/elife-66493-fig7.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a10b/8253595/26378a7db6ee/elife-66493-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a10b/8253595/cbcbaacebf2d/elife-66493-fig1.jpg
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