Giordano E, Peluso I, Senger S, Furia M
Dipartimento di Genetica, Biologia Generale e Molecolare, Università di Napoli Federico II, I-80134 Napoli, Italy.
J Cell Biol. 1999 Mar 22;144(6):1123-33. doi: 10.1083/jcb.144.6.1123.
We report here the genetic, molecular, and functional characterization of the Drosophila melanogaster minifly (mfl) gene. Genetic analysis shows that mfl is essential for Drosophila viability and fertility. While P-element induced total loss-of-function mutations cause lethality, mfl partial loss-of-function mutations cause pleiotropic defects, such as extreme reduction of body size, developmental delay, hatched abdominal cuticle, and reduced female fertility. Morphological abnormalities characteristic of apoptosis are found in the ovaries, and a proportion of eggs laid by mfl mutant females degenerates during embryogenesis. We show that mfl encodes an ubiquitous nucleolar protein that plays a central role in ribosomal RNA processing and pseudouridylation, whose known eukaryotic homologues are yeast Cfb5p, rat NAP57 and human dyskerin, encoded by the gene responsible for the X-linked dyskeratosis congenita disease. mfl genetic analysis represents the first in vivo functional characterization of a member of this highly conserved gene family from higher eukaryotes. In addition, we report that mfl hosts an intron encoded box H/ACA snoRNA gene, the first member of this class of snoRNAs identified so far from Drosophila.
我们在此报告黑腹果蝇微小蝇(mfl)基因的遗传、分子及功能特征。遗传分析表明,mfl对果蝇的生存力和繁殖力至关重要。虽然P因子诱导的完全功能丧失突变会导致致死性,但mfl部分功能丧失突变会导致多效性缺陷,如体型极度缩小、发育延迟、腹部表皮孵化以及雌性繁殖力降低。在卵巢中发现了凋亡特征性的形态异常,并且mfl突变雌性所产的一部分卵在胚胎发育过程中会退化。我们表明,mfl编码一种普遍存在的核仁蛋白,该蛋白在核糖体RNA加工和假尿苷化中起核心作用,其已知的真核同源物是酵母Cfb5p、大鼠NAP57和人类dyskerin,后者由导致X连锁先天性角化不良疾病的基因编码。mfl的遗传分析代表了来自高等真核生物的这个高度保守基因家族成员的首次体内功能特征描述。此外,我们报告mfl含有一个内含子编码的盒H/ACA snoRNA基因,这是迄今为止从果蝇中鉴定出的此类snoRNAs的首个成员。