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尿苷酰化调节裂殖酵母 mRNA 衰变方向性。

Uridylation regulates mRNA decay directionality in fission yeast.

机构信息

Institute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, Warsaw, Poland.

Department of Biochemistry, Charité - Universitätsmedizin Berlin, Berlin, Germany.

出版信息

Nat Commun. 2024 Sep 27;15(1):8359. doi: 10.1038/s41467-024-50824-w.

DOI:10.1038/s41467-024-50824-w
PMID:39333464
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11436920/
Abstract

Cytoplasmic mRNA decay is effected by exonucleolytic degradation in either the 5' to 3' or 3' to 5' direction. Pervasive terminal uridylation is implicated in mRNA degradation, however, its functional relevance for bulk mRNA turnover remains poorly understood. In this study, we employ genome-wide 3'-RACE (gw3'-RACE) in the model system fission yeast to elucidate the role of uridylation in mRNA turnover. We observe widespread uridylation of shortened poly(A) tails, promoting efficient 5' to 3' mRNA decay and ensuring timely and controlled mRNA degradation. Inhibition of this uridylation process leads to excessive deadenylation and enhanced 3' to 5' mRNA decay accompanied by oligouridylation. Strikingly we found that uridylation of poly(A) tails and oligouridylation of non-polyadenylated substrates are catalysed by different terminal uridyltransferases Cid1 and Cid16 respectively. Our study sheds new light on the intricate regulatory mechanisms underlying bulk mRNA turnover, demonstrating the role of uridylation in modulating mRNA decay pathways.

摘要

细胞质 mRNA 的降解是通过 5' 到 3' 或 3' 到 5' 方向的外切核酸酶降解来实现的。普遍存在的末端尿苷酸化被牵连到 mRNA 降解中，然而，其对大量 mRNA 周转的功能相关性仍知之甚少。在这项研究中，我们在模型系统裂殖酵母中使用全基因组 3' - RACE（gw3'-RACE）来阐明尿苷酸化在 mRNA 周转中的作用。我们观察到缩短的 poly(A) 尾巴的广泛尿苷酸化，促进有效的 5' 到 3' mRNA 降解，并确保 mRNA 降解的及时和控制。抑制这个尿苷酸化过程会导致过度的去腺苷酸化和增强的 3' 到 5' mRNA 降解，伴随着寡尿苷酸化。引人注目的是，我们发现 poly(A) 尾巴的尿苷酸化和非多聚腺苷酸化底物的寡尿苷酸化分别由不同的末端尿苷转移酶 Cid1 和 Cid16 催化。我们的研究为大量 mRNA 周转的复杂调控机制提供了新的见解，证明了尿苷酸化在调节 mRNA 降解途径中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/721c/11436920/b2ebe8aa2a2c/41467_2024_50824_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/721c/11436920/535f6f381464/41467_2024_50824_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/721c/11436920/11cbd58b1728/41467_2024_50824_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/721c/11436920/1391802fcb2a/41467_2024_50824_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/721c/11436920/f1ecd60810ad/41467_2024_50824_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/721c/11436920/e1f55c0095d3/41467_2024_50824_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/721c/11436920/b2ebe8aa2a2c/41467_2024_50824_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/721c/11436920/535f6f381464/41467_2024_50824_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/721c/11436920/11cbd58b1728/41467_2024_50824_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/721c/11436920/1391802fcb2a/41467_2024_50824_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/721c/11436920/f1ecd60810ad/41467_2024_50824_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/721c/11436920/e1f55c0095d3/41467_2024_50824_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/721c/11436920/b2ebe8aa2a2c/41467_2024_50824_Fig6_HTML.jpg

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本文引用的文献

1
Pervasive mRNA uridylation in fission yeast is catalysed by both Cid1 and Cid16 terminal uridyltransferases.在裂殖酵母中，普遍存在的 mRNA 尿苷酸化是由 Cid1 和 Cid16 末端尿苷转移酶共同催化的。
PLoS One. 2023 May 23;18(5):e0285576. doi: 10.1371/journal.pone.0285576. eCollection 2023.
2
The proteomic landscape of genome-wide genetic perturbations.全基因组遗传扰动的蛋白质组学全景。
Cell. 2023 Apr 27;186(9):2018-2034.e21. doi: 10.1016/j.cell.2023.03.026. Epub 2023 Apr 19.
3
High-throughput proteomics of nanogram-scale samples with Zeno SWATH MS.
使用 Zen SWATH MS 对纳克级样本进行高通量蛋白质组学分析。
Elife. 2022 Nov 30;11:e83947. doi: 10.7554/eLife.83947.
4
Measuring the tail: Methods for poly(A) tail profiling.测量尾巴：聚（A）尾巴分析方法。
Wiley Interdiscip Rev RNA. 2023 Jan;14(1):e1737. doi: 10.1002/wrna.1737. Epub 2022 May 26.
5
Codon optimality-mediated mRNA degradation: Linking translational elongation to mRNA stability.密码子优化介导的 mRNA 降解：将翻译延伸与 mRNA 稳定性联系起来。
Mol Cell. 2022 Apr 21;82(8):1467-1476. doi: 10.1016/j.molcel.2022.03.032.
6
Functional profiling of long intergenic non-coding RNAs in fission yeast.裂殖酵母中长基因间非编码 RNA 的功能谱分析。
Elife. 2022 Jan 5;11:e76000. doi: 10.7554/eLife.76000.
7
Decoupling of degradation from deadenylation reshapes poly(A) tail length in yeast meiosis.去降解与去腺苷酸化解耦重塑了酵母减数分裂中的 poly(A) 尾长。
Nat Struct Mol Biol. 2021 Dec;28(12):1038-1049. doi: 10.1038/s41594-021-00694-3. Epub 2021 Dec 9.
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