【原】胚胎干细胞表现出mRNA异构体特异性翻译调控

Embryonic Stem Cells Exhibit mRNA Isoform Specific Translational Regulation.

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|核心内容：

许多mRNA的多种变体的存在是蛋白质多样性的主要贡献因素。

这些变体的加工是以细胞类型特定的方式严格控制的，并对基因表达控制有重大影响。

在这里，我们研究了胚胎干细胞(ESCs)和胚胎干细胞来源的神经前体细胞(NPC)中单个mRNA变体的差异翻译率，方法是将多聚体分析与RNA测序相结合。

我们发现，在ESCs和NPC中有相当数量的可检测到的mRNA变体，并且其中许多都表现出不同的特异性翻译率。

这与变异体UTR的差异有关，其中5'UTR起主导作用。不同的5'UTR有不同的RBP来协助参与调控该message RNA的翻译。不同的RBP复合物的翻译效率可能不同。

我们认为，包含替代UTR的mRNA变体受到不同的转录后调控。

这可能是由于调节翻译速率的miRNA和蛋白质结合位点（resemble enhancer in DNA?）的存在或不存在。

这突出了当使用mRNA水平作为蛋白质丰度读数时解决翻译速率的重要性。

进一步的分析表明，在ESCs和NPC的多聚体部分上存在许多带注释的非编码mRNAs。

我们认为，将多聚体分离与RNA测序相结合是分析细胞内多种不同RNA翻译状态的一种有用的方法。

Fig 1. Polysome profiling of ESCs and NPCs

原文摘要：

The presence of multiple variants for many mRNAs is a major contributor to protein diversity. 

The processing of these variants is tightly controlled in a cell-type specific manner and has a significant impact on gene expression control. 

Here we investigate the differential translation rates of individual mRNA variants in embryonic stem cells (ESCs) and in ESC derived Neural Precursor Cells (NPCs) using polysome profiling coupled to RNA sequencing. 

We show that there are a significant number of detectable mRNA variants in ESCs and NPCs and that many of them show variant specific translation rates. 

This is correlated with differences in the UTRs of the variants with the 5'UTR playing a predominant role. 

We suggest that mRNA variants that contain alternate UTRs are under different post-transcriptional controls. 

This is likely due to the presence or absence of miRNA and protein binding sites that regulate translation rate. 

This highlights the importance of addressing translation rate when using mRNA levels as a read out of protein abundance. 

Additional analysis shows that many annotated non-coding mRNAs are present on the polysome fractions in ESCs and NPCs. 

We believe that the use of polysome fractionation coupled to RNA sequencing is a useful method for analysis of the translation state of many different RNAs in the cell.

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参考文献：https://storage./plos-corpus-prod/10.1371/journal.pone.0143235/1/pone.0143235.pdf?X-Goog-Algorithm=GOOG4-RSA-SHA256&X-Goog-Credential=wombat-sa%40plos-prod.iam.gserviceaccount.com%2F20201220%2Fauto%2Fstorage%2Fgoog4_request&X-Goog-Date=20201220T081250Z&X-Goog-Expires=3600&X-Goog-SignedHeaders=host&X-Goog-Signature=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