Mitochondrial RNA editing in trypanosomes: small RNAs in control.
Mitochondrial RNA editing in trypanosomes: small RNAs in control.
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DOI：
10.1016/j.biochi.2014.01.003
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发表时间：
2014-05
期刊：
影响因子：
3.9
通讯作者：
Aphasizheva I
中科院分区：
文献类型：
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作者：
Aphasizhev R;Aphasizheva I
锥虫中的线粒体mRNA编辑是一种转录后加工途径，从而将尿苷残基（Us）插入信使RNA前体中或从信使RNA前体中删除。通过纠正移码，引入起始和终止密码子，并经常添加大部分编码序列，编辑恢复了开放的阅读框架，为原始编码的mRNA。在单个前体mRNA中可能存在数百个编辑事件，通常间隔几个核苷酸，其中U插入的数量超过U缺失约10倍。线粒体基因组由约50个大环和数千个小环组成。链状的大环和小环被包装成称为动质体的致密结构;大环产生rRNA和mRNA前体，而向导RNA（gRNA）主要由小环产生，尽管在动质体物种中已经鉴定出不同数量的大环编码的gRNA。向导RNA通过与前体mRNA杂交并形成一系列错配来指定插入或缺失的U的位置和数量。这些50-60个核苷酸（nt）分子被RET 1 TUTase 3′尿苷化，并通过与gRNA结合复合物（GRBC）结合而稳定。RNA编辑核心复合物（RECC）催化mRNA切割、U-插入或缺失以及连接的编辑反应。为了在线粒体翻译中发挥作用，前体mRNA必须进一步通过多聚腺苷酸化/尿苷酸化进行编辑后3′修饰。最近的研究揭示了mRNA编辑和多聚腺苷酸化复合物的高度复合性及其与翻译机制的相互作用。在这里，我们专注于RNA编辑的机制及其与编辑前和编辑后3′ mRNA修饰和gRNA成熟途径的功能耦合。
Mitochondrial mRNA editing in trypanosomes is a posttranscriptional processing pathway thereby uridine residues (Us) are inserted into, or deleted from, messenger RNA precursors. By correcting frameshifts, introducing start and stop codons, and often adding most of the coding sequence, editing restores open reading frames for mitochondrially-encoded mRNAs. There can be hundreds of editing events in a single pre-mRNA, typically spaced by few nucleotides, with U-insertions outnumbering U-deletions by approximately 10-fold. The mitochondrial genome is composed of ~50 maxicircles and thousands of minicircles. Catenated maxi- and mini-circles are packed into a dense structure called the kinetoplast; maxicircles yield rRNA and mRNA precursors while guide RNAs (gRNAs) are produced predominantly from minicircles, although varying numbers of maxicircle-encoded gRNAs have been identified in kinetoplastids species. Guide RNAs specify positions and the numbers of inserted or deleted Us by hybridizing to premRNA and forming series of mismatches. These 50-60 nucleotide (nt) molecules are 3′ uridylated by RET1 TUTase and stabilized via association with the gRNA binding complex (GRBC). Editing reactions of mRNA cleavage, U-insertion or deletion, and ligation are catalyzed by the RNA editing core complex (RECC). To function in mitochondrial translation, pre-mRNAs must further undergo post-editing 3′ modification by polyadenylation/ uridylation. Recent studies revealed a highly compound nature of mRNA editing and polyadenylation complexes and their interactions with the translational machinery. Here we focus on mechanisms of RNA editing and its functional coupling with pre- and post-editing 3′ mRNA modification and gRNA maturation pathways.