LRPPRC/SLIRP suppresses PNPase-mediated mRNA decay and promotes polyadenylation in human mitochondria.
LRPPRC/SLIRP suppresses PNPase-mediated mRNA decay and promotes polyadenylation in human mitochondria.
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DOI：
10.1093/nar/gks506
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发表时间：
2012-09
影响因子：
14.9
通讯作者：
Suzuki T
中科院分区：
文献类型：
--
作者：
Chujo T;Ohira T;Sakaguchi Y;Goshima N;Nomura N;Nagao A;Suzuki T
在人类线粒体中，10种mRNA是由线粒体DNA重链转录的长多顺反子前体产生的，理论上产生相同拷贝数的mRNA分子。然而，这些mrna的稳态水平存在很大差异。通过对HeLa细胞中mRNA的绝对定量，我们发现所有线粒体mRNA种类的拷贝数在每个细胞6000到51000分子之间，表明线粒体积极调节mRNA代谢。此外，线粒体mrna的拷贝数与其细胞半衰期相关。先前，半衰期较长的mrna被LRPPRC/SLIRP复合物所稳定，我们发现LRPPRC/SLIRP复合物与mrna的编码序列共转录结合。我们观察到LRPPRC/SLIRP复合物抑制了由PNPase和SUV3介导的3 '外核溶解mRNA降解。此外，LRPPRC在体外促进线粒体多聚(A)聚合酶（MTPAP）介导的mrna的聚腺苷化。这些发现为理解人类线粒体mRNA代谢的分子机制提供了一个框架。
In human mitochondria, 10 mRNAs species are generated from a long polycistronic precursor that is transcribed from the heavy chain of mitochondrial DNA, in theory yielding equal copy numbers of mRNA molecules. However, the steady-state levels of these mRNAs differ substantially. Through absolute quantification of mRNAs in HeLa cells, we show that the copy numbers of all mitochondrial mRNA species range from 6000 to 51 000 molecules per cell, indicating that mitochondria actively regulate mRNA metabolism. In addition, the copy numbers of mitochondrial mRNAs correlated with their cellular half-life. Previously, mRNAs with longer half-lives were shown to be stabilized by the LRPPRC/SLIRP complex, which we find that cotranscriptionally binds to coding sequences of mRNAs. We observed that the LRPPRC/SLIRP complex suppressed 3′ exonucleolytic mRNA degradation mediated by PNPase and SUV3. Moreover, LRPPRC promoted the polyadenylation of mRNAs mediated by mitochondrial poly(A) polymerase (MTPAP) in vitro. These findings provide a framework for understanding the molecular mechanism of mRNA metabolism in human mitochondria.
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影响因子：
14.9
作者：
Cline SD;Lodeiro MF;Marnett LJ;Cameron CE;Arnold JJ
通讯作者：
Arnold JJ
影响因子：
14.9
作者：
Minczuk M;He J;Duch AM;Ettema TJ;Chlebowski A;Dzionek K;Nijtmans LG;Huynen MA;Holt IJ
通讯作者：
Holt IJ
影响因子：
64.8
作者：
OJALA, D;MONTOYA, J;ATTARDI, G
通讯作者：
ATTARDI, G
影响因子：
4.5
作者：
Bratic, Ana;Wredenberg, Anna;Larsson, Nils-Goeran
通讯作者：
Larsson, Nils-Goeran
影响因子：
4.8
作者：
Nagaike, T;Suzuki, T;Ueda, T
通讯作者：
Ueda, T