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外显子连接复合体依赖的 mRNA 定位与纤毛发生过程中的中心体组织有关。

Exon junction complex dependent mRNA localization is linked to centrosome organization during ciliogenesis.

机构信息

Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Ecole Normale Supérieure, CNRS, INSERM, PSL Research University, Paris, France.

Institute of Parasitology, Biology Centre, Czech Academy of Sciences, Ceske Budejovice, Czech Republic.

出版信息

Nat Commun. 2021 Mar 1;12(1):1351. doi: 10.1038/s41467-021-21590-w.

DOI:10.1038/s41467-021-21590-w
PMID:33649372
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7921557/
Abstract

Exon junction complexes (EJCs) mark untranslated spliced mRNAs and are crucial for the mRNA lifecycle. An imbalance in EJC dosage alters mouse neural stem cell (mNSC) division and is linked to human neurodevelopmental disorders. In quiescent mNSC and immortalized human retinal pigment epithelial (RPE1) cells, centrioles form a basal body for ciliogenesis. Here, we report that EJCs accumulate at basal bodies of mNSC or RPE1 cells and decline when these cells differentiate or resume growth. A high-throughput smFISH screen identifies two transcripts accumulating at centrosomes in quiescent cells, NIN and BICD2. In contrast to BICD2, the localization of NIN transcripts is EJC-dependent. NIN mRNA encodes a core component of centrosomes required for microtubule nucleation and anchoring. We find that EJC down-regulation impairs both pericentriolar material organization and ciliogenesis. An EJC-dependent mRNA trafficking towards centrosome and basal bodies might contribute to proper mNSC division and brain development.

摘要

外显子连接复合物 (EJCs) 标记未翻译的剪接 mRNA，对 mRNA 生命周期至关重要。EJC 剂量的不平衡改变了小鼠神经干细胞 (mNSC) 的分裂，与人类神经发育障碍有关。在静止的 mNSC 和永生化的人视网膜色素上皮 (RPE1) 细胞中，中心体形成纤毛发生的基体。在这里，我们报告 EJCs 在 mNSC 或 RPE1 细胞的基体上积累，并在这些细胞分化或恢复生长时减少。高通量 smFISH 筛选鉴定出两种在静止细胞中在中心体积累的转录本，NIN 和 BICD2。与 BICD2 相反，NIN 转录本的定位依赖于 EJC。NIN mRNA 编码中心体的核心组成部分，对于微管的核形成和锚定至关重要。我们发现 EJC 的下调会损害中心体周围物质的组织和纤毛发生。EJC 依赖性 mRNA 向中心体和基体的运输可能有助于 mNSC 的正确分裂和大脑发育。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdb/7921557/ba7cd76d80da/41467_2021_21590_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdb/7921557/9994059a4274/41467_2021_21590_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdb/7921557/070a7fc2d764/41467_2021_21590_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdb/7921557/c33493e736e3/41467_2021_21590_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdb/7921557/ba7cd76d80da/41467_2021_21590_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdb/7921557/6201a2e741dd/41467_2021_21590_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdb/7921557/20d4f8176d9f/41467_2021_21590_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdb/7921557/31389f72c8bc/41467_2021_21590_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdb/7921557/9994059a4274/41467_2021_21590_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdb/7921557/070a7fc2d764/41467_2021_21590_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdb/7921557/c33493e736e3/41467_2021_21590_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcdb/7921557/ba7cd76d80da/41467_2021_21590_Fig7_HTML.jpg

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