EVOLUTIONARY CONSERVATION OF THE HUMAN NUCLEOLAR PROTEIN FIBRILLARIN AND ITS FUNCTIONAL EXPRESSION IN YEAST

EVOLUTIONARY CONSERVATION OF THE HUMAN NUCLEOLAR PROTEIN FIBRILLARIN AND ITS FUNCTIONAL EXPRESSION IN YEAST
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DOI:
10.1083/jcb.113.4.715
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发表时间:
1991-05-01
影响因子:
7.8
通讯作者:
TOLLERVEY, D
TOLLERVEY, D
中科院分区:
生物学1区
文献类型:
--
作者:
JANSEN, RP;HURT, EC;TOLLERVEY, D

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NOP1是酵母中必需的核核蛋白,与小核核RNA相关,是核糖体生物发生所必需的。我们从HeLa cDNA文库中克隆了人核仁蛋白纤原蛋白。人类的纤维蛋白与酵母的NOP1有70%的相同,并且由于人类或非洲爪蟾的纤维蛋白都可以补充酵母的NOP1 -突变体,因此它们也是功能上的同源物。人纤维蛋白定位于酵母核仁并与酵母小核仁rna结合。这表明真核生物纤维蛋白内核仁结合和核仁功能所需的信号从酵母到人类是保守的。然而,人纤维蛋白在酵母中仅部分互补,导致温度敏感生长,同时改变rRNA加工和异常的核形态。人类纤维蛋白突变体的一个抑制因子被分离出来,并发现在人类核仁蛋白的单个氨基酸位置内定位。酵母nop1-株表达爪蟾蛋白或人纤原蛋白或人纤原蛋白抑制因子的生长速度与其高效、正确加工前rrna的能力密切相关。这些发现首次证明脊椎动物纤维蛋白在体内核糖体RNA加工中起作用。
NOP1 is an essential nucleolar protein in yeast that is associated with small nucleolar RNA and required for ribosome biogenesis. We have cloned the human nucleolar protein, fibrillarin, from a HeLa cDNA library. Human fibrillarin is 70% identical to yeast NOP1 and is also the functional homologue since either human or Xenopus fibrillarin can complement a yeast nop1- mutant. Human fibrillarin is localized in the yeast nucleolus and associates with yeast small nucleolar RNAs. This shows that the signals within eucaryotic fibrillarin required for nucleolar association and nucleolar function are conserved from yeast to man. However, human fibrillarin only partially complements in yeast resulting in a temperature-sensitive growth, concomitantly altered rRNA processing and aberrant nuclear morphology. A suppressor of the human fibrillarin ts-mutant was isolated and found to map intragenically at a single amino acid position of the human nucleolar protein. The growth rate of yeast nop1- strains expressing Xenopus or human fibrillarin or the human fibrillarin suppressor correlates closely with their ability to efficiently and correctly process pre-rRNA. These findings demonstrate for the first time that vertebrate fibrillarin functions in ribosomal RNA processing in vivo.