Milne C A, Hodgkin J
Medical Research Council, Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK.
Curr Biol. 1999 Nov 4;9(21):1243-6. doi: 10.1016/s0960-9822(99)80504-1.
Post-transcriptional gene processing by RNA-binding proteins (RBPs) has crucial roles during development [1] [2]. Here, we report the identification of ETR-1 (ELAV-type RNA-binding protein), a muscle-specific RBP in the nematode Caenorhabditis elegans. ETR-1 is related to the family of RBPs defined by the protein ELAV, which is essential for neurogenesis in the fruit fly Drosophila; members of the family possess two consecutive RNA recognition motifs (RRMs) separated from a third, carboxy-terminal RRM by a tether region of variable length [3] [4] [5] [6]. Its closest homologue, CUG-binding protein (CUG-bp), is a human RBP that has been implicated in the disease myotonic dystrophy and binds CUG repeats in the 3' untranslated region (UTR) of the mRNA for myotonic dystrophy protein kinase (DMPK) [7] [8]. Inactivation of etr-1 by RNA-mediated interference resulted in embryonic lethality. Embryos failed to elongate and became paralysed, a phenotype characteristic of C. elegans Pat mutants, which are defective in muscle formation and function [9]. The data indicate that etr-1 is essential for muscle development in C. elegans, perhaps by playing a role in post-transcriptional processing of some muscle component, and thus suggesting a possible conservation of gene function with human CUG-bp.
RNA结合蛋白（RBPs）介导的转录后基因加工在发育过程中起着关键作用[1][2]。在此，我们报告了线虫秀丽隐杆线虫中一种肌肉特异性RBP——ETR-1（ELAV型RNA结合蛋白）的鉴定。ETR-1与由ELAV蛋白定义的RBP家族相关，ELAV蛋白对果蝇的神经发生至关重要；该家族成员拥有两个连续的RNA识别基序（RRMs），它们通过可变长度的连接区域与第三个羧基末端RRM分开[3][4][5][6]。其最接近的同源物，CUG结合蛋白（CUG-bp），是一种人类RBP，与强直性肌营养不良症有关，并且结合强直性肌营养不良蛋白激酶（DMPK）mRNA的3'非翻译区（UTR）中的CUG重复序列[7][8]。通过RNA介导的干扰使etr-1失活导致胚胎致死。胚胎无法伸长并变得瘫痪，这是秀丽隐杆线虫Pat突变体的特征性表型，这些突变体在肌肉形成和功能方面存在缺陷[9]。数据表明，etr-1对秀丽隐杆线虫的肌肉发育至关重要，可能是通过在某些肌肉成分的转录后加工中发挥作用，从而提示与人类CUG-bp可能存在基因功能的保守性。
