Comparative parallel analysis of RNA ends identifies mRNA substrates of a tRNA splicing endonuclease-initiated mRNA decay pathway
Comparative parallel analysis of RNA ends identifies mRNA substrates of a tRNA splicing endonuclease-initiated mRNA decay pathway
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DOI：
10.1073/pnas.2020429118
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发表时间：
2021-03-09
影响因子：
11.1
通讯作者：
van Hoof, Ambro
中科院分区：
文献类型：
--
作者：
Hurtig, Jennifer E.;Steiger, Michelle A.;van Hoof, Ambro
真核生物共享一个保守的信使RNA （mRNA）衰变途径，其中大量mRNA被外核糖核酸酶降解。此外，更特殊的mRNA衰变途径是由特定位点的核内溶分裂引发的。转移RNA （tRNA）剪接内切酶（TSEN）因其从前tRNA中去除内含子的能力而被研究。最近有研究表明，TSEN中的单个氨基酸突变可引起桥小脑发育不全。最近的其他研究表明，TSEN还有其他功能，但这些功能的性质仍然不清楚。在这里，我们表明酵母TSEN切割编码线粒体蛋白的mrna的特定子集，并且切割位点部分由它们的序列决定。这为酵母TSEN的反直觉线粒体定位提供了解释。为了确定这些mRNA的靶位点，我们开发了一种“比较”（RNA末端的比较平行分析）生物信息学方法，该方法易于实施，并广泛适用于核糖核酸内切酶的研究。tRNA内切酶启动的降解与受调控的ire1依赖性mRNA的降解相似，表明共定位的mRNA特异性可能是多种真核细胞中本地化mRNA降解的重要决定因素。
Eukaryotes share a conserved messenger RNA (mRNA) decay pathway in which bulk mRNA is degraded by exoribonucleases. In addition, it has become clear that more specialized mRNA decay pathways are initiated by endonucleolytic cleavage at particular sites. The transfer RNA (tRNA) splicing endonuclease (TSEN) has been studied for its ability to remove introns from pre-tRNAs. More recently it has been shown that single amino acid mutations in TSEN cause pontocerebellar hypoplasia. Other recent studies indicate that TSEN has other functions, but the nature of these functions has remained obscure. Here we show that yeast TSEN cleaves a specific subset of mRNAs that encode mitochondrial proteins, and that the cleavage sites are in part determined by their sequence. This provides an explanation for the counterintuitive mitochondrial localization of yeast TSEN. To identify these mRNA target sites, we developed a "comPARE" (comparative parallel analysis of RNA ends) bioinformatic approach that should be easily implemented and widely applicable to the study of endoribonucleases. The similarity of tRNA endonuclease-initiated decay to regulated IRE1-dependent decay of mRNA suggests that mRNA specificity by colocalization may be an important determinant for the degradation of localized mRNAs in a variety of eukaryotic cells.