Guyot Boris, Arnaud Sylvie, Phothirath Phoukham, Rigal Dominique, Mouchiroud Guy
Centre de Génétique Moléculaire et Cellulaire, UMR CNRS 5534, Université Claude Bernard Lyon-1, Villeurbanne, France.
Platelets. 2002 Dec;13(8):459-64. doi: 10.1080/0953710021000059431.
Mona, also called Gads, is a molecular adapter that plays a key role in T-cell and platelet signalling by linking the adaptors Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa (Slp-76) and linker for activation of T cells (LAT) upon T-cell receptor and collagen receptor activation. Platelets express a specific form of Mona mRNA, called 1B, which is transcribed from a megakaryocyte-specific promoter. Mona 1B mRNA differ from 1A transcripts found in T cells and some myeloid cells only by the 5'UTR. We report here that 1B mRNA expressing cells do not express detectable amounts of Mona protein, in contrast to 1A expressing cells, and we show that 1B 5'UTR contains upstream open reading frames (uORFs). Mutating the corresponding uAUG restored efficient Mona translation, or that of an unrelated ORF. This suggested that Mona protein expression in 1B mRNA expressing cells is tightly controlled at the translational level. Accordingly, Mona protein was not detected in resting platelets. Strikingly, platelet activation by thrombin resulted in the rapid induction of Mona protein expression, suggesting that translation inhibition of 1B mRNA may be relieved in activated platelets.
莫娜（Mona），也称为加兹（Gads），是一种分子衔接蛋白，在T细胞受体和胶原受体激活时，通过连接含Src同源2结构域的76 kDa白细胞磷蛋白（Slp - 76）和T细胞激活连接蛋白（LAT），在T细胞和血小板信号传导中发挥关键作用。血小板表达一种特定形式的莫娜mRNA，称为1B，它由巨核细胞特异性启动子转录而来。莫娜1B mRNA与在T细胞和一些髓样细胞中发现的1A转录本仅在5'非翻译区有所不同。我们在此报告，与表达1A的细胞相比，表达1B mRNA的细胞不表达可检测量的莫娜蛋白，并且我们表明1B 5'非翻译区包含上游开放阅读框（uORF）。突变相应的uAUG可恢复莫娜或无关开放阅读框的有效翻译。这表明在表达1B mRNA的细胞中，莫娜蛋白表达在翻译水平受到严格控制。因此，在静息血小板中未检测到莫娜蛋白。引人注目的是，凝血酶激活血小板导致莫娜蛋白表达迅速诱导，这表明在活化血小板中1B mRNA的翻译抑制可能被解除。
