Poly（A）結(jié)合蛋白（PolyA tail binding proteins,，PABPs）在mRNA的多聚腺苷化,、維持mRNA穩(wěn)定性和翻譯調(diào)節(jié)過(guò)程中起重要作用,。具有合適長(zhǎng)度的Poly（A）是mRNA出核翻譯的前提,，Poly（A）解聚的mRNA會(huì)被迅速降解,。在酵母細(xì)胞的細(xì)胞核中主要有兩種Poly（A）結(jié)合蛋白,，Pab1p和Nab2p,，mRNA出核后，Nab2p被Pab1p置換,，再返回細(xì)胞核,，因此胞質(zhì)內(nèi)主要的Poly（A）結(jié)合蛋白是Pab1p。
在純化的釀酒酵母系統(tǒng)中,，只提供Pab1p和Nab2p都可以單獨(dú)維持mRNA的正常Poly（A）結(jié)構(gòu),，Pab1p與Nab2p不具有顯著同源性，在結(jié)合mRNA的時(shí)候這兩種蛋白如何分工,，這種機(jī)制的目前還不清楚,。
本文中，研究人員通過(guò)體內(nèi)和體外的一系列實(shí)驗(yàn)發(fā)現(xiàn),，外切酶體亞基Rrp6p有調(diào)節(jié)Poly（A）長(zhǎng)度的作用,，其機(jī)制是通過(guò)抑制Poly（A）聚合酶Trf4p來(lái)阻止成熟的mRNA繼續(xù)延長(zhǎng)。此外Rrp6p還具有引導(dǎo)Poly（A）結(jié)合蛋白定位在新生Poly（A）的作用,。當(dāng)Pab1p作為細(xì)胞內(nèi)主要的Poly（A）結(jié)合蛋白時(shí),，Nab2p只有在缺少Rrp6p的時(shí)候才起作用，這是因?yàn)镽rp6p可以與Nab2p相互作用,，使后者從Poly（A）上脫落下來(lái),。Nab2p脫落的mRNA有可能迅速出核進(jìn)行翻譯，也有可能因?yàn)槊撓佘栈到?。研究者認(rèn)為,，這是細(xì)胞中控制mRNA前體豐度的一種機(jī)制。（生物谷 Bioon.com ）
doi:10.1016/j.molcel.2012.05.005
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Rrp6p Controls mRNA Poly(A) Tail Length and Its Decoration with Poly(A) Binding Proteins
Manfred Schmid, Mathias Bach Poulsen, Pawel Olszewski, Vicent Pelechano, Cyril Saguez, Ishaan Gupta, Lars M. Steinmetz, Claire Moore, Torben Heick Jensen
Poly(A) (pA) tail binding proteins (PABPs) control mRNA polyadenylation, stability, and translation. In a purified system, S. cerevisiae PABPs, Pab1p and Nab2p, are individually sufficient to provide normal pA tail length. However, it is unknown how this occurs in more complex environments. Here we find that the nuclear exosome subunit Rrp6p counteracts the in vitro and in vivo extension of mature pA tails by the noncanonical pA polymerase Trf4p. Moreover, PABP loading onto nascent pA tails is controlled by Rrp6p; while Pab1p is the major PABP, Nab2p only associates in the absence of Rrp6p. This is because Rrp6p can interact with Nab2p and displace it from pA tails, potentially leading to RNA turnover, as evidenced for certain pre-mRNAs. We suggest that a nuclear mRNP surveillance step involves targeting of Rrp6p by Nab2p-bound pA-tailed RNPs and that pre-mRNA abundance is regulated at this level.
