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内质网应激时小 RNA 的差异加工。

Differential processing of small RNAs during endoplasmic reticulum stress.

机构信息

Department of Molecular and Cell Pathophysiology, Institute of General Pathology and Pathophysiology, Moscow, Russia.

Institute of Information Transmission Problems (Kharkevich Institute) of the Russian Academy of Sciences, Moscow, Russia.

出版信息

Sci Rep. 2017 Apr 13;7:46080. doi: 10.1038/srep46080.

DOI:10.1038/srep46080
PMID:28452371
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5408347/
Abstract

The accumulation of misfolded proteins in the endoplasmic reticulum (ER) lumen due to the disruption of the homeostatic system of the ER leads to the induction of the ER stress response. Cellular stress-induced pathways globally transform genes expression on both the transcriptional and post-transcriptional levels with small RNA involvement as regulators of the stress response. The modulation of small RNA processing might represent an additional layer of a complex stress response program. However, it is poorly understood. Here, we studied changes in expression and small RNAs processing upon ER stress in Jurkat T-cells. Induced by ER-stress, depletion of miRNAs among small RNA composition was accompanied by a global decrease of 3' mono-adenylated, mono-cytodinylated and a global increase of 3' mono-uridinylated miRNA isoforms. We observed the specific subset of differentially expressed microRNAs, and also the dramatic induction of 32-nt tRNA fragments precisely phased to 5' and 3' ends of tRNA from a subset of tRNA isotypes. The induction of these tRNA fragments was linked to Angiogenin RNase, which mediates translation inhibition. Overall, the global perturbations of the expression and processing of miRNAs and tiRNAs were the most prominent features of small RNA transcriptome changes upon ER stress.

摘要

内质网（ER）中由于内质网稳态系统破坏而导致错误折叠蛋白质的积累会引发 ER 应激反应。细胞应激诱导的途径在转录和转录后水平上全局改变基因表达，小 RNA 作为应激反应的调节剂参与其中。小 RNA 加工的调节可能代表复杂应激反应程序的附加层。然而，这方面的了解还很有限。在这里，我们研究了 Jurkat T 细胞中 ER 应激时的表达和小 RNA 加工变化。在 ER 应激诱导下，小 RNA 组成中的 miRNAs 耗竭伴随着 3'单腺苷酸化、单胞嘧啶酸化 miRNA 同工型的全面减少和 3'单尿嘧啶化 miRNA 同工型的全面增加。我们观察到特定的差异表达 microRNA 子集，以及特定的 tRNA 同工型的 tRNA 5'和 3'末端精确成相位的 32nt tRNA 片段的明显诱导。这些 tRNA 片段的诱导与血管生成素 RNase 有关，该酶介导翻译抑制。总的来说，miRNAs 和 tiRNAs 的表达和加工的全局扰动是 ER 应激时小 RNA 转录组变化的最显著特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1aac/5408347/73e3772e6574/srep46080-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1aac/5408347/bcff4aa7cf17/srep46080-f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1aac/5408347/8f4bc35c71ff/srep46080-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1aac/5408347/14dc134b0573/srep46080-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1aac/5408347/d57b41b8c0a3/srep46080-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1aac/5408347/73e3772e6574/srep46080-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1aac/5408347/bcff4aa7cf17/srep46080-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1aac/5408347/c477ee03d368/srep46080-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1aac/5408347/491c62da6e7b/srep46080-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1aac/5408347/8f4bc35c71ff/srep46080-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1aac/5408347/14dc134b0573/srep46080-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1aac/5408347/d57b41b8c0a3/srep46080-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1aac/5408347/73e3772e6574/srep46080-f7.jpg

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