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mRNA 稳定性因子 Khd4 定义了病原体中膜运输的特定 mRNA 调节子。

The mRNA stability factor Khd4 defines a specific mRNA regulon for membrane trafficking in the pathogen .

机构信息

Institute of Microbiology, Cluster of Excellence on Plant Sciences, Heinrich Heine University Düsseldorf, Düsseldorf 40204, Germany.

Biologisch-Medizinisches Forschungszentrum, Heinrich Heine University Düsseldorf, Düsseldorf 40204, Germany.

出版信息

Proc Natl Acad Sci U S A. 2023 Aug 22;120(34):e2301731120. doi: 10.1073/pnas.2301731120. Epub 2023 Aug 17.

DOI:10.1073/pnas.2301731120
PMID:37590419
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10450656/
Abstract

Fungal pathogens depend on sophisticated gene expression programs for successful infection. A crucial component is RNA regulation mediated by RNA-binding proteins (RBPs). However, little is known about the spatiotemporal RNA control mechanisms during fungal pathogenicity. Here, we discover that the RBP Khd4 defines a distinct mRNA regulon to orchestrate membrane trafficking during pathogenic development of . By establishing hyperTRIBE for fungal RBPs, we generated a comprehensive transcriptome-wide map of Khd4 interactions in vivo. We identify a defined set of target mRNAs enriched for regulatory proteins involved, e.g., in GTPase signaling. Khd4 controls the stability of target mRNAs via its cognate regulatory element AUACCC present in their 3' untranslated regions. Studying individual examples reveals a unique link between Khd4 and vacuole maturation. Thus, we uncover a distinct role for an RNA stability factor defining a specific mRNA regulon for membrane trafficking during pathogenicity.

摘要

真菌病原体依赖复杂的基因表达程序来成功感染。一个关键组成部分是由 RNA 结合蛋白 (RBP) 介导的 RNA 调控。然而，关于真菌致病性过程中的时空 RNA 控制机制知之甚少。在这里，我们发现 RBP Khd4 定义了一个独特的 mRNA 调节子，以协调致病发育过程中的膜运输。通过建立真菌 RBPs 的 hyperTRIBE，我们在体内生成了 Khd4 相互作用的全转录组图谱。我们确定了一组特定的靶 mRNA，它们富含参与调控蛋白，例如 GTPase 信号转导。Khd4 通过其在 3'非翻译区中存在的同源调节元件 AUACCC 来控制靶 mRNA 的稳定性。研究个别例子揭示了 Khd4 与液泡成熟之间的独特联系。因此，我们发现了 RNA 稳定性因子的一个独特作用，它为致病性过程中的膜运输定义了一个特定的 mRNA 调节子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bae/10450656/5a0561cb8bcf/pnas.2301731120fig07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bae/10450656/744813d3f16d/pnas.2301731120fig01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bae/10450656/a6fee44c3d26/pnas.2301731120fig02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bae/10450656/8aba9756a545/pnas.2301731120fig03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bae/10450656/242f6b88967b/pnas.2301731120fig04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bae/10450656/9cf58ab56f19/pnas.2301731120fig05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bae/10450656/a13814e56399/pnas.2301731120fig06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bae/10450656/5a0561cb8bcf/pnas.2301731120fig07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bae/10450656/744813d3f16d/pnas.2301731120fig01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bae/10450656/a6fee44c3d26/pnas.2301731120fig02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bae/10450656/8aba9756a545/pnas.2301731120fig03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bae/10450656/242f6b88967b/pnas.2301731120fig04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bae/10450656/9cf58ab56f19/pnas.2301731120fig05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bae/10450656/a13814e56399/pnas.2301731120fig06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bae/10450656/5a0561cb8bcf/pnas.2301731120fig07.jpg

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