The pioneer round of translation ensures proper targeting of ER and mitochondrial proteins.

The pioneer round of translation ensures proper targeting of ER and mitochondrial proteins.
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先锋轮翻译确保了ER和线粒体蛋白的正确靶向。

DOI:
10.1093/nar/gkab1098
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发表时间:
2021-12-02
影响因子:
14.9
通讯作者:
Kim YK
Kim YK
中科院分区:
生物学2区
文献类型:
--
作者:
Park J;Chang J;Hwang HJ;Jeong K;Lee HJ;Ha H;Park Y;Lim C;Woo JS;Kim YK

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新合成的mRNA的先驱(或第一)轮翻译主要由核帽结合复合物(CBC)介导。在多核糖体相关和CBC结合的转录本的全转录组分析中,我们确定RN 7SL 1,信号识别颗粒(SRP)的非编码RNA组分,作为CBC的相互作用伙伴。直接CBC-SRP相互作用防止来自核糖体-新生链复合物(RNC)-SRP复合物的多肽的异常表达,直到后者被适当地递送到内质网。这种监视的失败会导致错误折叠的蛋白质在不适当的细胞内位置的异常表达,导致胞质应激反应。这种监视途径还通过在编码线粒体蛋白的mRNA上错误组装的RNC-SRP来阻断蛋白质合成。因此,我们的研究结果揭示了一个监视途径,其中先锋翻译确保适当的内质网和线粒体蛋白的靶向。
The pioneer (or first) round of translation of newly synthesized mRNAs is largely mediated by a nuclear cap-binding complex (CBC). In a transcriptome-wide analysis of polysome-associated and CBC-bound transcripts, we identify RN7SL1, a noncoding RNA component of a signal recognition particle (SRP), as an interaction partner of the CBC. The direct CBC–SRP interaction safeguards against abnormal expression of polypeptides from a ribosome–nascent chain complex (RNC)–SRP complex until the latter is properly delivered to the endoplasmic reticulum. Failure of this surveillance causes abnormal expression of misfolded proteins at inappropriate intracellular locations, leading to a cytosolic stress response. This surveillance pathway also blocks protein synthesis through RNC–SRP misassembled on an mRNA encoding a mitochondrial protein. Thus, our results reveal a surveillance pathway in which pioneer translation ensures proper targeting of endoplasmic reticulum and mitochondrial proteins.
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