俄亥俄大學(xué)的科學(xué)家進(jìn)行的新研究顯示，會(huì)破壞某些蛋白質(zhì)之信使RNA (mRNA)的酵素PMR1,，在細(xì)胞受到環(huán)境壓力期間,，保護(hù)mRNA。這種反應(yīng)會(huì)使癌細(xì)胞在化療和放射治療中存活下來(lái),。
這種酵素會(huì)依附在某些mRNA分子正,，并且遺留了一顆插著保險(xiǎn)拴的手榴彈。這些mRNAs傳遞著制造某些特殊蛋白質(zhì)的信息,，當(dāng)命令到達(dá)時(shí),，細(xì)胞必須停止手邊的工作來(lái)制造這些蛋白質(zhì)。但是當(dāng)制造的指令抵達(dá)時(shí),，同時(shí)也將手榴彈的保險(xiǎn)拴拉開(kāi),，使酵素開(kāi)始破壞mRNA，因此迅速地抑制這種蛋白質(zhì)的生產(chǎn),。
這項(xiàng)新研究發(fā)現(xiàn),，在面臨這種環(huán)境壓力的情況下，這種依附在mRNA上的酵素PMR1,，也會(huì)幫助mRNA在細(xì)胞中搭建臨時(shí)的遮雨棚,，又稱(chēng)為壓力顆粒(stress granules)，mRNA可以在壓力顆粒中受到保護(hù),，使環(huán)境壓力結(jié)束后,，蛋白質(zhì)的生產(chǎn)可以迅速地恢復(fù)。
壓力顆粒是mRNA 和蛋白質(zhì)短暫的聚集處,，當(dāng)細(xì)胞面臨不利的環(huán)境條件如饑餓,、氧氣過(guò)低或接受化療或放射治療時(shí)，mRNA 和蛋白質(zhì)就會(huì)暫避于壓力顆粒中,。
這項(xiàng)研究結(jié)果發(fā)表于12月號(hào)的Molecular and Cellular Biology中,，研究作者是俄亥俄州立大學(xué)的Daniel R. Schoenberg教授。藉由了解PMR1和類(lèi)似的酵素如何產(chǎn)生壓力顆粒,，研究人員將可以學(xué)習(xí)如何抑制癌細(xì)胞的防護(hù)機(jī)制,，并使癌細(xì)胞無(wú)法對(duì)抗癌癥治療。
部分英文原文：
Polysome-Bound Endonuclease PMR1 Is Targeted to Stress Granules via Stress-Specific Binding to TIA-1
The generalized process of mRNA decay involves deadenylation followed by release from translating polysomes, decapping, and exonuclease decay of the mRNA body. In contrast the mRNA endonuclease PMR1 forms a selective complex with its translating substrate mRNA, where it initiates decay by cleaving within the mRNA body. In stressed cells the phosphorylation of the subunit of eukaryotic initiation factor 2 causes translating mRNAs to accumulate with stalled 48S subunits in large subcellular structures termed stress granules (SGs), wherein mRNAs undergo sorting for reinitiation, storage, or decay. Given the unique relationship between translation and PMR1-mediated mRNA decay, we examined the impact of stress-induced dissociation of polysomes on this process. Arsenite stress disrupts the polysome binding of PMR1 and its substrate mRNA but has no impact on the critical tyrosine phosphorylation of PMR1, its association with substrate mRNA, or its association with the functional 680-kDa mRNP complex in which it normally resides on polysomes. We show that arsenite stress drives PMR1 into an RNase-resistant complex with TIA-1, and we identify a distinct domain in the N terminus of PMR1 that facilitates its interaction with TIA-1. Finally, we show that arsenite promotes the delayed association of PMR1 with SGs under conditions which cause tristetraprolin and butyrate response factor 1, proteins that facilitate exonucleolytic mRNA, to exit SGs.
