Endoribonucleolytic Cleavage of m6A-Containing RNAs by RNase P/MRP Complex
Endoribonucleolytic Cleavage of m6A-Containing RNAs by RNase P/MRP Complex
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DOI：
10.1016/j.molcel.2019.02.034
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发表时间：
2019-05-02
期刊：
影响因子：
16
通讯作者：
Kim, Yoon Ki
中科院分区：
文献类型：
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作者：
Park, Ok Hyun;Ha, Hongseok;Kim, Yoon Ki
n -6-甲基腺苷（m(6)A）是rna中含量最多的内部修饰，在多种生物生理过程中发挥调控作用。尽管m(6) a介导的基因调控具有重要作用，但其分子机制尚不清楚。在这里，我们发现含有m(6)A的rna可以通过YTHDF2 （m(6)A解读蛋白）、HRSP12（适配器蛋白）和RNase P/MRP（核糖核酸内酶）进行核糖核酸内裂解。我们证明了HRSP12作为连接YTHDF2和RNase P/MRP的接头，引发YTHDF2结合的rna的快速降解。转录组分析表明，优先靶向核糖核酸内裂解的m(6)A rna在ythdf2结合位点的上游和下游分别有一个hrsp12结合位点和一个RNase P/ mrp导向的裂解位点。我们还发现含有m(6) a的环状rna的一个子集以hrsp12依赖的方式与YTHDF2结合，并被RNase P/MRP选择性下调。因此，我们的数据将RNase P/MRP的已知功能扩展到核糖核酸内裂解m(6)A rna。
N-6-methyladenosine (m(6)A) is the most abundant internal modification in RNAs and plays regulatory roles in a variety of biological and physiological processes. Despite its important roles, the molecular mechanism underlying m(6)A-mediated gene regulation is poorly understood. Here, we show that m(6)A-containing RNAs are subject to endoribonucleolytic cleavage via YTHDF2 (m(6)A reader protein), HRSP12 (adaptor protein), and RNase P/MRP (endoribonucleases). We demonstrate that HRSP12 functions as an adaptor to bridge YTHDF2 and RNase P/MRP, eliciting rapid degradation of YTHDF2-bound RNAs. Transcriptome-wide analyses show that m(6)A RNAs that are preferentially targeted for endoribonucleolytic cleavage have an HRSP12-binding site and a RNase P/MRP-directed cleavage site upstream and downstream of the YTHDF2-binding site, respectively. We also find that a subset of m(6)A-containing circular RNAs associates with YTHDF2 in an HRSP12-dependent manner and is selectively downregulated by RNase P/MRP. Thus, our data expand the known functions of RNase P/MRP to endoribonucleolytic cleavage of m(6)A RNAs.