<br>一种分泌增强顺式调控靶向元件 (SECReTE)，参与 mRNA 定位和蛋白质合成。,PLOS Genetics

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一种分泌增强顺式调控靶向元件 (SECReTE)，参与 mRNA 定位和蛋白质合成。
PLOS Genetics ( IF 4.0 ) Pub Date : 2019-07-01 , DOI: 10.1371/journal.pgen.1008248
Osnat Cohen-Zontag ₁ , Camila Baez ₁ , Lisha Qiu Jin Lim ₁ , Tsviya Olender ₁ , Dvir Schirman ₁ , Dvir Dahary ₁ , Yitzhak Pilpel ₁ , Jeffrey E Gerst ₁

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编码分泌/膜蛋白 (mSMP) 的 mRNA 定位到内质网 (ER) 可能促进分泌蛋白的共翻译易位。然而，研究表明，真核生物中 mSMP 招募到 ER 的方式可以独立于核糖体、翻译控制和信号识别粒子，尽管其机制仍然很大程度上未知。在这里，我们鉴定了一个顺式作用的RNA序列基序，它增强了mSMP在ER中的定位，并且似乎增加了mRNA的稳定性以及分泌蛋白的合成和分泌。该基序被称为 SECReTE，代表分泌增强顺式调控靶向元件，富含编码在真核生物 ER 和原核生物内膜上翻译的分泌蛋白的 mRNA。 SECReTE 由 ≥10 个核苷酸三联体重复组成，每三个碱基富含嘧啶 (C/U)（即 NNY，其中 N = 任何核苷酸，Y = 嘧啶），并且可以存在于 mRNA 的非翻译区和编码区中。提高给定 mRNA（例如 SUC2、HSP150 和 CCW12）中 SECReTE 计数的同义突变会导致酵母中蛋白质分泌增加，而计数减少会导致分泌减少和生理缺陷。此外，将SECReTE添加到外源表达蛋白（例如GFP）的mRNA的3'UTR导致其从酵母细胞的分泌增加。因此，SECReTE 构成了一种新的 RNA 基序，可促进内质网定位的 mRNA 翻译和蛋白质分泌。

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A secretion-enhancing cis regulatory targeting element (SECReTE) involved in mRNA localization and protein synthesis.

The localization of mRNAs encoding secreted/membrane proteins (mSMPs) to the endoplasmic reticulum (ER) likely facilitates the co-translational translocation of secreted proteins. However, studies have shown that mSMP recruitment to the ER in eukaryotes can occur in a manner that is independent of the ribosome, translational control, and the signal recognition particle, although the mechanism remains largely unknown. Here, we identify a cis-acting RNA sequence motif that enhances mSMP localization to the ER and appears to increase mRNA stability, and both the synthesis and secretion of secretome proteins. Termed SECReTE, for secretion-enhancing cis regulatory targeting element, this motif is enriched in mRNAs encoding secretome proteins translated on the ER in eukaryotes and on the inner membrane of prokaryotes. SECReTE consists of ≥10 nucleotide triplet repeats enriched with pyrimidine (C/U) every third base (i.e. NNY, where N = any nucleotide, Y = pyrimidine) and can be present in the untranslated as well as the coding regions of the mRNA. Synonymous mutations that elevate the SECReTE count in a given mRNA (e.g. SUC2, HSP150, and CCW12) lead to an increase in protein secretion in yeast, while a reduction in count led to less secretion and physiological defects. Moreover, the addition of SECReTE to the 3'UTR of an mRNA for an exogenously expressed protein (e.g. GFP) led to its increased secretion from yeast cells. Thus, SECReTE constitutes a novel RNA motif that facilitates ER-localized mRNA translation and protein secretion.

更新日期：2019-08-03

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