16 Poly(A) Metabolism and Translation: The Closed-loop Model
16 Poly(A) Metabolism and Translation: The Closed-loop Model
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16 Poly(A) 代谢和翻译：闭环模型
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发表时间：
1996
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通讯作者：
A. Jacobson
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作者：
A. Jacobson
二十多年前，关于不同RNA的核糖核酸酶敏感性的实验导致认识到，真核信使RNA中存在不间断的聚腺苷酸(Poly[A])(Lim和Canellakis 1970；Darnell等人)。1971a，b；Edmonds et al.1971年；凯茨1971年；李等人。1971年)。现在人们已经认识到，几乎所有生物合成起源于核的mRNAs都含有一个3‘聚(A)尾巴。Poly(A)序列不是在基因内编码的(Philipson等人。1971年；Birnboim等人。1973年；雅各布森等人。1974)，但在涉及位点特异性切割和随后的聚腺苷酸化的加工反应中添加到新生的前mRNAs中。切割位点由一个高度保守的AAUAAA序列决定，通常5-30个核苷酸位于该位点，另一个保守程度较低的序列为3‘，有时为5’。裂解和多聚腺苷酸化依赖于聚(A)聚合酶和其他几个赋予反应特异性和可操作性的因素。有关多聚腺苷化的序列和因子要求的综述，见Wens(1990)、ProudFoot(1991)、Wahle和Keller(1992)以及Manley和ProudFoot(1994)。脉冲追逐实验表明，新合成的核多聚(A)的很大一部分在细胞质中是保守的(Puckett等人)。1975)。这些实验早期支持了异质核RNA(HnRNA)是mRNA的前体这一观点，并迫使人们得出结论，即聚(A)至少有一个功能肯定是细胞质的。本章提出了后一种结论有价值的证据，我在这一章中认为……
More than two decades ago, experiments on the ribonuclease susceptibility of different RNAs led to the realization that uninterrupted tracts of polyadenylic acid (poly[A]) are present within eukaryotic messenger RNAs (Lim and Canellakis 1970; Darnell et al. 1971a,b; Edmonds et al. 1971; Kates 1971; Lee et al. 1971). It is now well recognized that almost all mRNAs whose biosynthesis originates within nuclei contain a 3′ poly(A) tail. Poly(A) sequences are not encoded within genes (Philipson et al. 1971; Birnboim et al. 1973; Jacobson et al. 1974) but are added to nascent pre-mRNAs in a processing reaction that involves site-specific cleavage and subsequent polyadenylation. The site of cleavage is determined by a highly conserved AAUAAA sequence usually 5–30 nucleotides 5′ to the site and by other less well-conserved sequences 3′, and sometimes 5′, to the site. Cleavage and polyadenylation are dependent on poly(A) polymerase and several other factors that impart specificity and processivity to the reaction. For reviews on the sequence and factor requirements of polyadenylation, see Wickens (1990), Proudfoot (1991), Wahle and Keller (1992), and Manley and Proudfoot (1994). Pulse-chase experiments demonstrated that a large fraction of newly synthesized nuclear poly(A) was conserved in cytoplasmic mRNA (Puckett et al. 1975). These experiments provided early support for the notion that heterogeneous nuclear RNA (hnRNA) was the precursor to mRNA and also forced the conclusion that at least one function of poly(A) must be cytoplasmic. Evidence that the latter conclusion had merit is presented in this chapter, where I consider the...