Ribosome heterogeneity in Drosophila melanogaster gonads through paralog-switching.

Ribosome heterogeneity in Drosophila melanogaster gonads through paralog-switching.
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DOI:
10.1093/nar/gkab606
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发表时间:
2022-02-28
影响因子:
14.9
通讯作者:
Aspden JL
Aspden JL
中科院分区:
生物学2区
文献类型:
--
作者:
Hopes T;Norris K;Agapiou M;McCarthy CGP;Lewis PA;O'Connell MJ;Fontana J;Aspden JL

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核糖体长期以来被认为是同质的大分子机器,但最近的证据表明它们是异质的,可以专门调节翻译。在这里,我们的特点是核糖体蛋白质异质性在4个组织的果蝇。我们发现,睾丸和卵巢含有最异质的核糖体群体,这是通过旁系同源富集和旁系同源转换的组合发生的。我们已经通过冷冻电镜解析了从体内组织中纯化的核糖体的结构,揭示了睾丸和卵巢80 S核糖体精确核糖体排列的差异。旁系同源对的氨基酸组成及其在核糖体外部的定位差异表明旁系同源转换可以改变核糖体表面,使不同的蛋白质能够调节翻译。在人类中也发现了一个睾丸特异性旁系同源转换对,这表明这是核糖体异质性的保守位点。总的来说,这项工作使我们能够提出,mRNA翻译可能通过核糖体异质性在性腺中进行调节,提供了一种潜在的核糖体专门化手段。
Ribosomes have long been thought of as homogeneous macromolecular machines, but recent evidence suggests they are heterogeneous and could be specialised to regulate translation. Here, we have characterised ribosomal protein heterogeneity across 4 tissues of Drosophila melanogaster. We find that testes and ovaries contain the most heterogeneous ribosome populations, which occurs through a combination of paralog-enrichment and paralog-switching. We have solved structures of ribosomes purified from in vivo tissues by cryo-EM, revealing differences in precise ribosomal arrangement for testis and ovary 80S ribosomes. Differences in the amino acid composition of paralog pairs and their localisation on the ribosome exterior indicate paralog-switching could alter the ribosome surface, enabling different proteins to regulate translation. One testis-specific paralog-switching pair is also found in humans, suggesting this is a conserved site of ribosome heterogeneity. Overall, this work allows us to propose that mRNA translation might be regulated in the gonads through ribosome heterogeneity, providing a potential means of ribosome specialisation.
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