Global 3′ UTR shortening has a limited effect on protein abundance in proliferating T cells
Global 3′ UTR shortening has a limited effect on protein abundance in proliferating T cells
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DOI：
10.1038/ncomms6465
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发表时间：
2014-11-01
影响因子：
16.6
通讯作者：
Zavolan, Mihaela
中科院分区：
文献类型：
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作者：
Gruber, Andreas R.;Martin, Georges;Zavolan, Mihaela
选择性多聚腺苷酸化是一种细胞机制，其产生在其3'非翻译区（3' UTR）中不同的mRNA同种型。多聚腺苷酸化位点使用的变化已被描述后，诱导在静息细胞增殖，但这种现象的潜在机制和功能意义仍然在很大程度上未知。为了理解缩短的3'UTR同种型在生理环境中的功能后果，我们使用3'末端测序和定量质谱法来确定鼠和人幼稚和活化T细胞中的多聚腺苷酸化位点使用、mRNA和蛋白质水平。尽管增殖细胞中的3' UTR缩短在人和小鼠之间是保守的，但是直向同源基因不表现出替代3' UTR同种型的相似表达。我们通常发现3'UTR缩短并不伴随着mRNA和蛋白水平的相应变化。这表明，尽管3'UTR缩短可能导致RNA结合蛋白相互作用组的变化，但它对蛋白质输出的影响有限。
Alternative polyadenylation is a cellular mechanism that generates mRNA isoforms differing in their 3' untranslated regions (3' UTRs). Changes in polyadenylation site usage have been described upon induction of proliferation in resting cells, but the underlying mechanism and functional significance of this phenomenon remain largely unknown. To understand the functional consequences of shortened 3' UTR isoforms in a physiological setting, we used 3' end sequencing and quantitative mass spectrometry to determine polyadenylation site usage, mRNA and protein levels in murine and human naive and activated T cells. Although 3' UTR shortening in proliferating cells is conserved between human and mouse, orthologous genes do not exhibit similar expression of alternative 3' UTR isoforms. We generally find that 3' UTR shortening is not accompanied by a corresponding change in mRNA and protein levels. This suggests that although 3' UTR shortening may lead to changes in the RNA-binding protein interactome, it has limited effects on protein output.