Embryonic lethal abnormal visual RNA-binding proteins involved in growth, differentiation, and posttranscriptional gene expression
Embryonic lethal abnormal visual RNA-binding proteins involved in growth, differentiation, and posttranscriptional gene expression
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DOI：
10.1086/514866
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发表时间：
1997-08-01
影响因子：
9.8
通讯作者：
Keene, JD
中科院分区：
文献类型：
--
作者：
Antic, D;Keene, JD
尽管果蝇的ELAV最近被认为与选择性剪接有关（Koushika等人，1996），但脊椎动物的ELAV蛋白转录、转录后和翻译区域的基因表达受到严格控制，因此神经细胞也可能在细胞质中起作用，调节其翻译水平。虽然转录是调控基因表达的主要水平，但已经很清楚特异性mrna或其转换率（Levine etal. 1993；高andkeene1996； Jainetal. 1997; Myeretal. 1997）。一些水平的转录后RNA加工在调节不稳定mRNA的最终结果中起重要作用，物种编码多种调节细胞生长和分化的蛋白质。合成蛋白质生产。真核premRNA的加工，包括聚腺苷化、旋盖和剪接- c-fos mRNA，例如，代表了先前静止的细胞周期激活的早期步骤，以及rna的转运，影响成熟mRNA的翻译可用性。此外，局部细胞和这一步骤的持续时间受到c-fos mRNA快速降解的限制（Schiavi et al. 1992，细胞质mRNA的化、稳定性和可翻译性影响了其中的定量和定性方面）。导致这种和许多其他mRNA物种快速周转的信号包括最终基因表达的penof。尽管许多基因已被证明影响核苷酸，AUUUA，通常存在于不稳定mrna的3个utr的多个拷贝中（有关综述，参见Chen通过转录调控的组织发育，相对较少的基因涉及和Shyu 1995的调控，以及其中的参考文献）。在某些情况下，这个序列足以在转录后水平上使正常的长寿命细胞生长或分化。正如所料，rna -蛋白相互作用的关键mRNA，如b-珠蛋白mRNA，是不稳定的（Shaw and Kamen 1986）。mrna在转录后基因表达调控中的内在不稳定性。在果蝇的遗传筛选中发现了一种基因，其产物在RNA加工水平上编码蛋白质，诱导细胞增殖或分化，这是一种重要的调节机制。这个基因被命名为elav（发音为ella），可以对胚胎致死性异常视觉表型的c-fos、c-myc、Id转录v等蛋白的表达进行精确的时间控制，对调节因子或葡萄糖转运蛋白GLUT1的发育和维持至关重要。如下所述，ELAV蛋白与神经系统特异性结合（Campos et al. 1985; Robinow and White 1988）。ELAV蛋白及其脊椎动物同源物代表位于3个utr中的富含au的序列元件，这提高了这些蛋白可以改变RNA结合蛋白RRM （RNA识别基序）超家族的一个亚家族的命运的可能性（在Kenan结合mrna中进行了综述）。事实上，广泛表达的32-kD蛋白与mRNA的稳定性有关，并且已知结合等。1991；Burd and Dreyfuss 1994)。在果蝇中的遗传发现已经扩展到对人类ELAV的研究，最近通过应用分子、生化和组合选择方法，在c-myc和c-fos mrna的3个utr中发现了富含au的序列（Vakalopoulou et al. 1991）。总之，这些可能是一个ELAV蛋白（Myer et al. 1997）。研究将ELAV蛋白与生长和分化过程中基因表达的转录后调控联系起来。
Cell growth and differentiation in mammalian tissues Whereas Drosophila ELAV recently has been implicated in alternative splicing (Koushika et al. 1996), neuare regulated by tight control of gene expression at the transcriptional, posttranscriptional, and translational ronal ELAV proteins from vertebrates may also act in the cytoplasm to modulate either the translation of spelevels. Although transcription is the primary level of regulation of gene expression, it has become clear that cific mRNAs or their rate of turnover (Levine et al. 1993; GaoandKeene1996; Jainetal. 1997; Myeretal. 1997). several levels of posttranscriptional RNA processing play important roles in regulating the final outcome of Unstable mRNA species encode a variety of proteins that regulatecellgrowthanddifferentiation. Thesynthesisof protein production. Processing of eukaryotic premRNA, including polyadenylation, capping, and splic- c-fos mRNA, for instance, represents an early step in the activation of the cell cycle in previously quiescent ing, as well as transport of RNAs, affect the availability of mature mRNA for translation. In addition, the local- cells, and the duration of this step is limited by rapid degradation of c-fos mRNA (Schiavi et al. 1992, and ization, stability, and translatability of cytoplasmic mRNAs affect both quantitative and qualitative aspects references therein). A signal that confers rapid turnover of this and many other mRNA species includes the penof final gene expression.Although many genes have been shown to influence tanucleotide, AUUUA, often present in multiple copies in the 3 UTRs of unstable mRNAs (for review see Chen organismal development through transcriptional regulation, relatively few have been implicated in regulation of and Shyu 1995, and references therein). In some cases, this sequence is sufficient to make a normally long-lived cell growth or differentiation at posttranscriptional levels. As might be expected, RNA-protein interactions play key mRNA, such as the b-globin mRNA, unstable (Shaw and Kamen 1986). The intrinsic instability of mRNAs regulatory roles in postranscriptional gene expression. One gene whose product acts at the level of RNA processing encoding proteins that induce cell proliferation or differentiation represents an important regulatory mechanism was discovered in a genetic screen of the fruit fly Drosophila melanogaster. This gene, named elav (pronounced ella- and allows for precise temporal control of the expression of such proteins as c-fos, c-myc, the Id transcriptional vee) for the embryonic lethal abnormal visual phenotype, is essential for the development and maintenance of the regulator, or the glucose transporter, GLUT1. As described below, the ELAV proteins bind specifically to nervous system (Campos et al. 1985; Robinow and White 1988). ELAV protein and its vertebrate homologues repre- AU-rich sequence elements located in 3 UTRs, raising the possibility that these proteins can alter the fate of sent a subfamily of the RRM (RNA recognition motif) superfamily of RNA-binding proteins (reviewed in Kenan bound mRNAs. Indeed, a widely expressed 32-kD protein implicated in mRNA stability and known to bind et al. 1991; Burd and Dreyfuss 1994). Genetic findings in the fly have been extended to the study of human ELAV to AU-rich sequences in 3 UTRs of c-myc and c-fos mRNAs (Vakalopoulou et al. 1991) was recently shown proteins by application of molecular, biochemical, and combinatorial selection methods. Together, these ap- to be an ELAV protein (Myer et al. 1997). proaches link ELAV proteins to posttranscriptional regulation of gene expression during growth and differentiation ELAV Genes in …