Trypanosome RNAEditing Substrate Binding Complex integrity and function depends on the upstream action of RESC10.
Trypanosome RNAEditing Substrate Binding Complex integrity and function depends on the upstream action of RESC10.
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DOI：
10.1093/nar/gkab129
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发表时间：
2021-04-06
影响因子：
14.9
通讯作者：
Read LK
中科院分区：
文献类型：
--
作者：
Dubey AP;Tylec BL;McAdams NM;Sortino K;Read LK
线粒体mRNA的尿苷插入/缺失编辑是动质体的特征，包括布氏锥虫。编辑由反式作用gRNA指导，并由相关的RNA编辑核心复合物（RECCs）催化。非催化RNA编辑底物结合复合物（RESC）协调RECC，gRNA和mRNA之间的相互作用。RESC是一种动态复合物，包括GRBC（向导RNA结合复合物）和异质REMC（RNA编辑介体复合物）。在这里，我们表明，RESC 10是一个必不可少的，低丰度，RNA结合蛋白，表现出RNA酶敏感和RNA酶不敏感的相互作用与RESC蛋白，虽然其最小的在体内与RESC 13的相互作用。RESC 10 RNAi导致广泛的RESC解体，包括破坏GRBC内蛋白质-蛋白质相互作用，以及GRBC的mRNA消耗和REMC上的积累。在单核苷酸分辨率下对线粒体RNA的分析揭示了转录物特异性效应：RESC 10显著影响泛编辑的RPS 12 mRNA中的编辑进程，但对于具有内部起始gRNA的mRNA中的编辑起始至关重要，这表明这些RNA类别的不同起始机制。RESC 10缺失细胞中编辑暂停的位点与先前研究的RESC蛋白敲低的位点之间的相关性表明，RESC 10在这些因子的上游起作用，RESC在促进尿苷插入和缺失RECs之间的转换方面特别重要。
Uridine insertion/deletion editing of mitochondrial mRNAs is a characteristic feature of kinetoplastids, including Trypanosoma brucei. Editing is directed by trans-acting gRNAs and catalyzed by related RNA Editing Core Complexes (RECCs). The non-catalytic RNA Editing Substrate Binding Complex (RESC) coordinates interactions between RECC, gRNA and mRNA. RESC is a dynamic complex comprising GRBC (Guide RNA Binding Complex) and heterogeneous REMCs (RNA Editing Mediator Complexes). Here, we show that RESC10 is an essential, low abundance, RNA binding protein that exhibits RNase-sensitive and RNase-insensitive interactions with RESC proteins, albeit its minimal in vivo interaction with RESC13. RESC10 RNAi causes extensive RESC disorganization, including disruption of intra-GRBC protein–protein interactions, as well as mRNA depletion from GRBC and accumulation on REMCs. Analysis of mitochondrial RNAs at single nucleotide resolution reveals transcript-specific effects: RESC10 dramatically impacts editing progression in pan-edited RPS12 mRNA, but is critical for editing initiation in mRNAs with internally initiating gRNAs, pointing to distinct initiation mechanisms for these RNA classes. Correlations between sites at which editing pauses in RESC10 depleted cells and those in knockdowns of previously studied RESC proteins suggest that RESC10 acts upstream of these factors and that RESC is particularly important in promoting transitions between uridine insertion and deletion RECCs.
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DOI：
10.1007/978-1-60761-738-9_22
发表时间：
2010
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.5
作者：
Hashimi, Hassan;Cicova, Zdenka;Lukes, Julius
通讯作者：
Lukes, Julius
影响因子：
4.5
作者：
Hashimi, Hassan;Zikova, Alena;Lukes, Julius
通讯作者：
Lukes, Julius
影响因子：
14.9
作者：
Koslowsky D;Sun Y;Hindenach J;Theisen T;Lucas J
通讯作者：
Lucas J
影响因子：
4.8
作者：
Carnes, Jason;Soares, Carmen Zelaya;Stuart, Kenneth
通讯作者：
Stuart, Kenneth