The mRNA 3′ poly(A) tail plays a critical role in regulating both mRNA translation and turnover. It is bound by the cytoplasmic poly(A) binding protein (PABPC), an evolutionarily conserved protein that can interact with translation factors and mRNA decay machineries to regulate gene expression. Mammalian PABPC1, the prototypical PABPC, is expressed in most tissues and interacts with eukaryotic translation initiation factor 4G (eIF4G) to stimulate translation in specific contexts. In this study, we uncovered a new mammalian PABPC, which we named neural PABP (neuPABP), as it is predominantly expressed in the brain. neuPABP maintains a unique architecture as compared with other PABPCs, containing only two RNA recognition motifs (RRMs) and maintaining a unique N-terminal domain of unknown function. neuPABP expression is activated in neurons as they mature during synaptogenesis, where neuPABP localizes to the soma and postsynaptic densities. neuPABP interacts with the noncoding RNA BC1, as well as mRNAs coding for ribosomal and mitochondrial proteins. However, in contrast to PABPC1, neuPABP does not associate with actively translating mRNAs in the brain. In keeping with this, we show that neuPABP has evolved such that it does not bind eIF4G and as a result fails to support protein synthesis in vitro. Taken together, these results indicate that mammals have expanded their PABPC repertoire in the brain and propose that neuPABP may support the translational repression of select mRNAs.

中文翻译：

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发现具有独特性质的哺乳动物神经特异性聚 (A) 结合蛋白

mRNA 3' Poly(A) 尾在调节 mRNA 翻译和周转中发挥着关键作用。它与细胞质多聚腺苷酸结合蛋白 (PABPC) 结合，这是一种进化上保守的蛋白质，可以与翻译因子和 mRNA 衰变机制相互作用以调节基因表达。哺乳动物 PABPC1 是典型的 PABPC，在大多数组织中表达，并与真核翻译起始因子 4G (eIF4G) 相互作用，以刺激特定环境中的翻译。在这项研究中，我们发现了一种新的哺乳动物 PABPC，我们将其命名为神经 PABP (neuPABP)，因为它主要在大脑中表达。与其他 PABPC 相比，neuPABP 保持了独特的结构，仅包含两个 RNA 识别基序 (RRM)，并保持了一个未知功能的独特 N 端结构域。当神经元在突触发生过程中成熟时，neuPABP 表达在神经元中被激活，其中 neuPABP 定位于胞体和突触后密度。neuPABP 与非编码 RNA BC1 以及编码核糖体和线粒体蛋白的 mRNA 相互作用。然而，与 PABPC1 相比，neuPABP 并不与大脑中主动翻译的 mRNA 相关。与此相一致，我们表明 neuPABP 已经进化到不结合 eIF4G，因此无法支持体外蛋白质合成。总而言之，这些结果表明哺乳动物已经扩展了其大脑中的 PABPC 库，并提出 neuPABP 可能支持选定 mRNA 的翻译抑制。