hnRNP A2 selectively binds the cytoplasmic transport sequence of myelin basic protein mRNA
hnRNP A2 selectively binds the cytoplasmic transport sequence of myelin basic protein mRNA
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DOI：
10.1021/bi9800247
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发表时间：
1998-05-12
期刊：
影响因子：
2.9
通讯作者：
Smith, R
中科院分区：
文献类型：
--
作者：
Hoek, KS;Kidd, GJ;Smith, R
在非洲爪蟾和果蝇卵子发生中涉及的蛋白质以及体细胞中的一些蛋白质中，已经证明了mRNA在极细胞的细胞质中的分离。假设消息的矢量传输通常负责这种本地化。编码中枢神经系统髓鞘碱性蛋白的mRNA被选择性地转运到少突胶质细胞突起的远端，在那里它被锚定到髓鞘膜并被翻译。这种转运依赖于3'-非翻译区（RTS）的21个核苷酸的顺式作用片段。现在已经从大鼠大脑提取物中分离出了与这一顺式作用片段结合的蛋白质。一组6个35 - 42-kDa蛋白质与掺入RTS的35个碱基的寡核糖核苷酸结合，但不与具有相同组成但随机序列的几种寡核糖核苷酸结合，从而建立了RTS中碱基序列的特异性。这些蛋白质中最丰富的已被确定，通过Edman测序的胰蛋白酶肽和质谱，作为异质核核糖核蛋白（hnRNP）A2，一个36 kDa的成员的蛋白质家族，主要是，但不是唯一的，核内。这种蛋白质在大鼠大脑和睾丸样品中含量最高，在其他组织中含量较低。通过使用反相HPLC将其与其他多肽分离，并显示保留与RTS的优先缔合。在培养的少突胶质细胞，hnRNP A2被证明通过共聚焦显微镜分布在整个细胞核，细胞索马，和过程。
Segregation of mRNAs in the cytoplasm of polar cells has been demonstrated for proteins involved in Xenopus and Drosophila oogenesis, and for some proteins in somatic cells. It is assumed that vectorial transport of the messages is generally responsible for this localization. The mRNA encoding the basic protein of central nervous system myelin is selectively transported to the distal ends of the processes of oligodendrocytes, where it is anchored to the myelin membrane and translated. This transport is dependent on a 21-nucleotide cis-acting segment of the 3'-untranslated region (RTS). Proteins that bind to this cis-acting segment have now been isolated from extracts of rat brain. A group of six 35-42-kDa proteins bind to a 35-base oligoribonucleotide incorporating the RTS, but not to several oligoribonucleotides with the same composition but randomized sequences, thus establishing specificity for the base sequence in the RTS. The most abundant of these proteins has been identified, by Edman sequencing of tryptic peptides and mass spectroscopy, as heterogeneous nuclear ribonucleoprotein (hnRNP) A2, a 36-kDa member of a family of proteins that are primarily, but not solely, intranuclear. This protein was most abundant in samples from rat brain and testis, with lower amounts in other tissues. It was separated from the other polypeptides by using reverse-phase HPLC and shown to retain preferential association with the RTS. In cultured oligodendrocytes, hnRNP A2 was demonstrated by confocal microscopy to be distributed throughout the nucleus, cell soma, and processes.