Significant roles in RNA-binding for the amino-terminal regions of Drosophila Pumilio and Nanos.

IF 4 2区 生物学 Q1 GENETICS & HEREDITY
PLoS Genetics Pub Date : 2025-03-31 eCollection Date: 2025-03-01 DOI:10.1371/journal.pgen.1011616
Tammy H Wharton, Mohammad Marhabaie, Robin P Wharton
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引用次数: 0

Abstract

The Drosophila Pumilio (Pum) and Nanos (Nos) RNA-binding proteins govern abdominal segmentation in the early embryo, as well as a variety of other events during development. They bind together to a compound Nanos Response Element (NRE) present in thousands of maternal mRNAs in the ovary and embryo, including hunchback (hb) mRNA, thereby regulating poly-adenylation, translation, and stability. Many studies support a model in which mRNA recognition and effector recruitment are carried out by distinct regions of each protein. The well-ordered Pum and Nos RNA-binding domains (RBDs) are sufficient to specifically recognize NREs; the larger intrinsically disordered N-terminal regions (NTRs) of each protein have been thought to act by recruiting mRNA regulators. Here we use yeast interaction assays and experiments testing the regulation of hb mRNA in vivo to show that the NTRs play a significant role in recognition of the NRE, acting via two mechanisms. First, the Pum and Nos NTRs interact in trans to promote assembly of the Pum/Nos/NRE ternary complex. Second, the Pum NTR acts via an unknown mechanism in cis, modifying NRE recognition by its RBD. The ability of the NTR to alter binding to the NRE is conserved in human Pum2.

在果蝇和纳米果蝇氨基末端区域rna结合中的重要作用。
果蝇Pumilio (Pum)和Nanos (Nos) rna结合蛋白在早期胚胎中控制腹部分割,以及发育过程中的各种其他事件。它们结合在一起的复合纳米反应元件(NRE)存在于卵巢和胚胎中数千种母体mRNA中,包括驼背mRNA (hb),从而调节多聚腺苷化、翻译和稳定性。许多研究支持一种模型,其中mRNA识别和效应招募是由每种蛋白质的不同区域进行的。有序的Pum和Nos rna结合域(rbd)足以特异性识别NREs;每个蛋白质的较大的内在无序n端区域(NTRs)被认为是通过招募mRNA调节因子来起作用的。在这里,我们使用酵母相互作用分析和实验来测试hb mRNA在体内的调节,表明NTRs在NRE的识别中发挥重要作用,通过两种机制起作用。首先,Pum和Nos ntr在反式中相互作用,促进Pum/Nos/NRE三元配合物的组装。其次,泵NTR通过一种未知的顺式机制起作用,通过其RBD修改NRE识别。NTR改变与NRE结合的能力在人类Pum2中是保守的。
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
PLoS Genetics
PLoS Genetics GENETICS & HEREDITY-
自引率
2.20%
发文量
438
期刊介绍: PLOS Genetics is run by an international Editorial Board, headed by the Editors-in-Chief, Greg Barsh (HudsonAlpha Institute of Biotechnology, and Stanford University School of Medicine) and Greg Copenhaver (The University of North Carolina at Chapel Hill). Articles published in PLOS Genetics are archived in PubMed Central and cited in PubMed.
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