SRP RNA 的生物发生受转录过程中获得的 RNA 折叠中间产物的调节。

The Biogenesis of SRP RNA Is Modulated by an RNA Folding Intermediate Attained during Transcription.

机构信息

Institute for Quantitative Biosciences-QB3, University of California, Berkeley, Berkeley, CA, USA; Okazaki Institute for Integrative Bioscience and Institute for Molecular Science, National Institutes of Natural Science, Tokyo, Japan; Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kanazawa 920-1192, Japan.

Institute for Quantitative Biosciences-QB3, University of California, Berkeley, Berkeley, CA, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.

出版信息

Mol Cell. 2020 Jan 16;77(2):241-250.e8. doi: 10.1016/j.molcel.2019.10.006. Epub 2019 Nov 6.

DOI:10.1016/j.molcel.2019.10.006

PMID:31706702

Abstract

The signal recognition particle (SRP), responsible for co-translational protein targeting and delivery to cellular membranes, depends on the native long-hairpin fold of its RNA to confer functionality. Since RNA initiates folding during its synthesis, we used high-resolution optical tweezers to follow in real time the co-transcriptional folding of SRP RNA. Surprisingly, SRP RNA folding is robust to transcription rate changes and the presence or absence of its 5'-precursor sequence. The folding pathway also reveals the obligatory attainment of a non-native hairpin intermediate (H1) that eventually rearranges into the native fold. Furthermore, H1 provides a structural platform alternative to the native fold for RNase P to bind and mature SRP RNA co-transcriptionally. Delays in attaining the final native fold are detrimental to the cell, altogether showing that a co-transcriptional folding pathway underpins the proper biogenesis of function-essential SRP RNA.

摘要

信号识别颗粒（SRP）负责将蛋白质靶向并递送至细胞膜，这依赖于其 RNA 的天然长发夹折叠来赋予功能。由于 RNA 在其合成过程中开始折叠，我们使用高分辨率光镊实时跟踪 SRP RNA 的共转录折叠。令人惊讶的是，SRP RNA 折叠对转录速率变化以及其 5'前体序列的存在与否具有鲁棒性。折叠途径还揭示了必需获得非天然发夹中间体 (H1)，该中间体最终重新排列成天然折叠。此外，H1 为 RNase P 提供了替代天然折叠的结构平台，以共转录方式结合和成熟 SRP RNA。延迟获得最终的天然折叠对细胞是有害的，这表明共转录折叠途径是功能必需的 SRP RNA 正确生物发生的基础。