The 3′-untranslated region of cytochrome oxidase II rnRNA functions in RNA editing of African trypanosomes exclusively as a cis guide RNA
The 3′-untranslated region of cytochrome oxidase II rnRNA functions in RNA editing of African trypanosomes exclusively as a cis guide RNA
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DOI：
10.1261/rna.7170705
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发表时间：
2005-01-01
期刊：
影响因子：
4.5
通讯作者：
Hajduk, SL
中科院分区：
文献类型：
--
作者：
Golden, DE;Hajduk, SL
锥虫中的RNA编辑是一种转录后过程，负责纠正许多线粒体mRNA的编码序列。尿苷通过酶级联从mRNA中特异性添加或缺失，其中预编辑的mRNA被特异性切割，尿苷被添加或去除，并且校正的mRNA被连接。这个过程是由RNA分子指导的，称为指导RNA（gRNA）。这类小的非编码RNA在RNA编辑中发挥作用的能力对这些生物体至关重要。通常，gRNA独立于其同源mRNA转录并退火以形成二元RNA复合物。该过程的例外可能是细胞色素氧化酶亚基II（COII）mRNA，因为尚未鉴定出编码反式作用gRNA的基因。使用体外编辑测定，我们发现COII的3'UTR确实起到了指导添加到COII I mRNA编码区的尿苷的位点和数量的作用。我们进一步表明，当与编辑底物邻接时，COII 3' UTR内的指导序列只能在COII编辑中起作用，这表明COII的3' UTR缺乏作为反式作用gRNA起作用所必需的序列或结构信息。虽然其他RNA已显示“指导”RNA加工反应，但我们发现COII 3'UTR指导其顺式同源mRNA的编辑是3'UTR的独特功能。这里描述的研究结果使我们提出了一个新的模型，在动质体gRNA的进化。
RNA editing in trypanosomes is a post-transcriptional process responsible for correcting the coding sequences of many mitochondrial mRNAs. Uridines are specifically added or deleted from mRNA by an enzymatic cascade in which a pre-edited mRNA is specifically cleaved, uridines are added or removed, and the corrected mRNA is ligated. The process is directed by RNA molecules, termed guide RNAs (gRNA). The ability of this class of small, noncoding RNA to function in RNA editing is essential for these organisms. Typically, gRNAs are transcribed independent of the their cognate mRNA and anneal to form a binary RNA complex. An exception for this process may be cytochrome oxidase subunit II (COII) mRNA since a gene encoding a transacting gRNA has not been identified. Using an in vitro editing assay we find that the 3' UTR of COII, indeed, functions as a guide for both the site and number of uridines added to the coding region of the COII I mRNA. We further show that the guiding sequence within the COII 3' UTR can only function in COII editing when contiguous with the editing substrate, indicating that the 3' UTR of COII lacks sequence or structure information necessary to function as a trans-acting gRNA. While other RNAs have been shown to "guide" RNA processing reactions, our discovery that the COII 3' UTR directs editing of its cognate mRNA in cis, is a unique function for a 3' UTR. The findings described here have led us to propose a new model for the evolution of gRNAs in kinetoplastids.