文献类型：期刊文献

英文题名：RNA-Seq analysis uncovers non-coding small RNA system of Mycobacterium neoaurum in the metabolism of sterols to accumulate steroid intermediates

作者：Liu, Min[1];Zhu, Zhan-Tao[1];Tao, Xin-Yi[1];Wang, Feng-Qing[1];Wei, Dong-Zhi[1]

机构：[1]E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Newworld Inst Biotechnol, Shanghai 200237, Peoples R China

年份：2016

卷号：15

外文期刊名：MICROBIAL CELL FACTORIES

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000374926800001)】；

基金：This research was financially supported by the Fundamental Research Funds for the Central Universities of China (222201414019), China Postdoctoral Science Foundation (2014M561427), National Natural Science Foundation of China (31500043, 31370080), National Special Fund for State Key Laboratory of Bioreactor Engineering (2060204), National Basic Research Program of China (973, Program No. 2012CB721103) and the National Major Science and Technology Projects of China (No. 2012ZX09304009). Thanks for Kang Yao for the assistance of RNA-seq.

语种：英文

外文关键词：Noncoding RNA; Small regulatory RNA; RNA sequencing; Steroid catabolism; Mycobacterium

摘要：Background: Understanding the metabolic mechanism of sterols to produce valuable steroid intermediates in mycobacterium by a noncoding small RNA (sRNA) view is still limited. In the work, RNA-seq was implemented to investigate the noncoding transcriptome of Mycobacterium neoaurum (Mn) in the transformation process of sterols to valuable steroid intermediates, including 9a-hydroxy-4-androstene-3,17-dione (9OHAD), 1,4-androstadiene-3,17-dione (ADD), and 22-hydroxy-23, 24-bisnorchola-1,4-dien-3-one (1,4-BNA). Results: A total of 263 sRNA candidates were predicted from the intergenic regions in Mn. Differential expression of sRNA candidates was explored in the wide type Mn with vs without sterol addition, and the steroid intermediate producing Mn strains vs wide type Mn with sterol addition, respectively. Generally, sRNA candidates were differentially expressed in various strains, but there were still some shared candidates with outstandingly upregulated or downregulated expression in these steroid producing strains. Accordingly, four regulatory networks were constructed to reveal the direct and/or indirect interactions between sRNA candidates and their target genes in four groups, including wide type Mn with vs without sterol addition, 9OHAD, ADD, and BNA producing strains vs wide type Mn with sterol addition, respectively. Based on these constructed networks, several highly focused sRNA candidates were discovered to be prevalent in the networks, which showed comprehensive regulatory roles in various cellular processes, including lipid transport and metabolism, amino acid transport and metabolism, signal transduction, cell envelope biosynthesis and ATP synthesis. To explore the functional role of sRNA candidates in Mn cells, we manipulated the overexpression of candidates 131 and 138 in strain Mn-9OHAD, which led to enhanced production of 9OHAD from 1.5- to 2.3-fold during 6 d' fermentation and a slight effect on growth rate. Conclusions: This study revealed the complex and important regulatory roles of noncoding small RNAs in the metabolism of sterols to produce steroid intermediates in Mn, further analysis of which will promote the better understanding about the molecular metabolism of these sRNA candidates and open a broad range of opportunities in the field.