Fasken Milo B, Corbett Anita H
Department of Biology, Emory University, 1510 Clifton Rd., NE RRC 1021, Atlanta, GA 30322, U.S.A.
RNA Dis. 2016;3(4). Epub 2016 Nov 7.
In recent years, the impairment of RNA binding proteins that play key roles in the post-transcriptional regulation of gene expression has been linked to numerous neurological diseases. These RNA binding proteins perform critical mRNA processing steps in the nucleus, including splicing, polyadenylation, and export. In many cases, these RNA binding proteins are ubiquitously expressed raising key questions about why only brain function is impaired. Recently, mutations in the gene, encoding an evolutionarily conserved, polyadenosine RNA binding protein, have been linked to a nonsyndromic form of autosomal recessive intellectual disability. Thus far, research on ZC3H14 and its Nab2 orthologs in budding yeast and reveals that ZC3H14/Nab2 is important for mRNA processing and neuronal patterning. Two recent studies now provide evidence that ZC3H14/Nab2 may function in the quality control of mRNA splicing and export and could help to explain the molecular defects that cause neuronal dysfunction and lead to an inherited form of intellectual disability. These studies on ZC3H14/Nab2 reveal new clues to the puzzle of why loss of the ubiquitously expressed ZC3H14 protein specifically affects neurons.
近年来，在基因表达的转录后调控中发挥关键作用的RNA结合蛋白的损伤与众多神经疾病有关。这些RNA结合蛋白在细胞核中执行关键的mRNA加工步骤，包括剪接、聚腺苷酸化和输出。在许多情况下，这些RNA结合蛋白广泛表达，这就引发了关于为何只有脑功能受损的关键问题。最近，编码一种进化上保守的聚腺苷酸RNA结合蛋白的基因发生突变，与一种常染色体隐性非综合征型智力残疾有关。到目前为止，对芽殖酵母中的ZC3H14及其Nab2直系同源物的研究表明，ZC3H14/Nab2对mRNA加工和神经元模式形成很重要。最近的两项研究现在提供了证据，表明ZC3H14/Nab2可能在mRNA剪接和输出的质量控制中发挥作用，并有助于解释导致神经元功能障碍并导致遗传性智力残疾形式的分子缺陷。这些关于ZC3H14/Nab2的研究揭示了为何广泛表达的ZC3H14蛋白的缺失会特异性影响神经元这一谜题的新线索。
