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用于监测自噬转录的基因工具盒。

A gene toolbox for monitoring autophagy transcription.

机构信息

Department of Pediatric Hemato-Oncology and Cell and Gene therapy, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.

Telethon Institute of Genetics and Medicine (TIGEM), Pozzuśoli, Naples, Italy.

出版信息

Cell Death Dis. 2021 Nov 2;12(11):1044. doi: 10.1038/s41419-021-04121-9.

Abstract

Autophagy is a highly dynamic and multi-step process, regulated by many functional protein units. Here, we have built up a comprehensive and up-to-date annotated gene list for the autophagy pathway, by combining previously published gene lists and the most recent publications in the field. We identified 604 genes and created main categories: MTOR and upstream pathways, autophagy core, autophagy transcription factors, mitophagy, docking and fusion, lysosome and lysosome-related genes. We then classified such genes in sub-groups, based on their functions or on their sub-cellular localization. Moreover, we have curated two shorter sub-lists to predict the extent of autophagy activation and/or lysosomal biogenesis; we next validated the "induction list" by Real-time PCR in cell lines during fasting or MTOR inhibition, identifying ATG14, ATG7, NBR1, ULK1, ULK2, and WDR45, as minimal transcriptional targets. We also demonstrated that our list of autophagy genes can be particularly useful during an effective RNA-sequencing analysis. Thus, we propose our lists as a useful toolbox for performing an informative and functionally-prognostic gene scan of autophagy steps.

摘要

自噬是一个高度动态和多步骤的过程,受许多功能蛋白单元的调节。在这里,我们通过结合以前发表的基因列表和该领域的最新出版物,为自噬途径构建了一个全面和最新的注释基因列表。我们确定了 604 个基因,并创建了主要类别:MTOR 和上游途径、自噬核心、自噬转录因子、线粒体自噬、对接和融合、溶酶体和溶酶体相关基因。然后,我们根据其功能或亚细胞定位将这些基因分类为子组。此外,我们还整理了两个较短的子列表来预测自噬激活和/或溶酶体发生的程度;我们接下来通过在禁食或 MTOR 抑制期间的细胞系中的实时 PCR 验证了“诱导列表”,鉴定出 ATG14、ATG7、NBR1、ULK1、ULK2 和 WDR45 是最小的转录靶标。我们还证明,我们的自噬基因列表在有效的 RNA-seq 分析中特别有用。因此,我们建议将我们的列表作为执行信息丰富且具有功能预后的自噬步骤基因扫描的有用工具包。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad48/8563709/533ee7738e23/41419_2021_4121_Fig1_HTML.jpg

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