酶介导的邻近标记揭示了有丝分裂期间mRNA向中心体的共翻译靶向。

Enzyme-mediated proximity labeling reveals the co-translational targeting of mRNA to the centrosome during mitosis.

作者信息

Wang Gang, Li Mo, Zou Peng

机构信息

Academy for Advanced Interdisciplinary Studies, PKU-Tsinghua Center for Life Science, Peking University Beijing 100871 China

Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital Beijing 100191 China

出版信息

RSC Chem Biol. 2025 Mar 26. doi: 10.1039/d4cb00155a.

Abstract

Subcellular RNA localization is a conserved mechanism in eukaryotic cells and plays critical roles in diverse physiological processes including cell proliferation, differentiation, and embryo development. Nevertheless, the characterization of centrosome-localized mRNAs remains underexplored due to technical difficulties. In this study, we utilize APEX2-mediated proximity labeling to map the centrosome-proximal transcriptome, identifying mRNA as a novel centrosome-localized transcript during mitosis. Using a combination of drug perturbation, truncation, deletion, and mutagenesis, we demonstrate that microtubule binding of nascent MBD1 polypeptides is required for centrosomal transport of mRNA. Our data also reveal that mRNA targeting efficiency is tightly linked to the coding sequence (CDS) length. Thus, our study provides a transcriptomic resource for future investigation of centrosome-localized RNAs and sheds light on mechanisms underlying mRNA centrosomal localization.

摘要

亚细胞RNA定位是真核细胞中的一种保守机制,在包括细胞增殖、分化和胚胎发育在内的多种生理过程中发挥关键作用。然而,由于技术困难,中心体定位mRNA的特征仍未得到充分探索。在本研究中,我们利用APEX2介导的邻近标记来绘制中心体近端转录组图谱,鉴定出mRNA是有丝分裂期间一种新的中心体定位转录本。通过药物扰动、截短、缺失和诱变相结合的方法,我们证明新生MBD1多肽的微管结合是mRNA中心体运输所必需。我们的数据还表明,mRNA靶向效率与编码序列(CDS)长度紧密相关。因此,我们的研究为未来中心体定位RNA的研究提供了一个转录组资源,并揭示了mRNA中心体定位的潜在机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f181/12135621/e1e07b89cf3f/d4cb00155a-f1.jpg

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