Poly(A)结合蛋白(PolyA tail binding proteins,PABPs)在mRNA的多聚腺苷化、维持mRNA稳定性和翻译调节过程中起重要作用。具有合适长度的Poly(A)是mRNA出核翻译的前提,Poly(A)解聚的mRNA会被迅速降解。在酵母细胞的细胞核中主要有两种Poly(A)结合蛋白,Pab1p和Nab2p,mRNA出核后,Nab2p被Pab1p置换,再返回细胞核,因此胞质内主要的Poly(A)结合蛋白是Pab1p。
在纯化的酿酒酵母系统中,只提供Pab1p和Nab2p都可以单独维持mRNA的正常Poly(A)结构,Pab1p与Nab2p不具有显着同源性,在结合mRNA的时候这两种蛋白如何分工,这种机制的目前还不清楚。
本文中,研究人员通过体内和体外的一系列实验发现,外切酶体亚基Rrp6p有调节Poly(A)长度的作用,其机制是通过抑制Poly(A)聚合酶Trf4p来阻止成熟的mRNA继续延长。此外Rrp6p还具有引导Poly(A)结合蛋白定位在新生Poly(A)的作用。当Pab1p作为细胞内主要的Poly(A)结合蛋白时,Nab2p只有在缺少Rrp6p的时候才起作用,这是因为Rrp6p可以与Nab2p相互作用,使后者从Poly(A)上脱落下来。Nab2p脱落的mRNA有可能迅速出核进行翻译,也有可能因为脱腺苷化而降解。研究者认为,这是细胞中控制mRNA前体丰度的一种机制。(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.