King P H, Levine T D, Fremeau R T, Keene J D
Department of Microbiology, Duke University Medical Center, Durham, North Carolina 27710.
J Neurosci. 1994 Apr;14(4):1943-52. doi: 10.1523/JNEUROSCI.14-04-01943.1994.
Mammalian cDNAs encoding a rat (Rel-N1) and a human (Hel-N1) neuronal RNA-binding protein have been cloned and characterized with respect to tissue specificity, neuroanatomical localization, and RNA binding specificity. Both proteins are highly similar to the product of the Drosophila elav gene, which is expressed in all neurons of the fly and is required for development of the nervous system. However, in situ hybridization of rat tissues demonstrated more restricted expression of Rel-N1 mRNA within a subset of neurons of the hippocampus, cortex, and other regions of the gray matter, but not in glial cells or white matter. In vitro RNA binding experiments demonstrated that Hel-N1 can bind to the 3' untranslated region (3' UTR) of Id mRNA, a transcript that encodes a helix-loop-helix transcriptional repressor that is abundantly expressed in undifferentiated neural precursors. Sequences characterized for Hel-N1 binding were also abundantly present in the 3' UTR of the Drosophila extramacrochaetae mRNA, which encodes an Id homolog. Thus, we have identified a potential link between a neuronal 3' UTR RNA-binding protein and regulatory transcription factors involved in neural development. These findings are interpreted in light of recent studies in which mRNA 3' UTRs were found to be important for the regulation of cell growth and differentiation.
编码大鼠(Rel-N1)和人类(Hel-N1)神经元RNA结合蛋白的哺乳动物cDNA已被克隆,并在组织特异性、神经解剖定位和RNA结合特异性方面进行了表征。这两种蛋白都与果蝇elav基因的产物高度相似,该基因在果蝇的所有神经元中表达,是神经系统发育所必需的。然而,大鼠组织的原位杂交显示Rel-N1 mRNA在海马体、皮质和其他灰质区域的一部分神经元中表达更受限,而在神经胶质细胞或白质中不表达。体外RNA结合实验表明,Hel-N1可以结合Id mRNA的3'非翻译区(3'UTR),Id mRNA是一种转录本,编码一种在未分化的神经前体中大量表达的螺旋-环-螺旋转录抑制因子。在果蝇extra macrochaetae mRNA的3'UTR中也大量存在被表征为Hel-N1结合的序列,该mRNA编码一种Id同源物。因此,我们确定了一种神经元3'UTR RNA结合蛋白与参与神经发育的调节转录因子之间的潜在联系。这些发现是根据最近的研究来解释的,在这些研究中发现mRNA 3'UTR对细胞生长和分化的调节很重要。