Polynucleotide phosphorylase: Not merely an RNase but a pivotal post-transcriptional regulator.
Polynucleotide phosphorylase: Not merely an RNase but a pivotal post-transcriptional regulator.
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DOI：
10.1371/journal.pgen.1007654
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发表时间：
2018-10
期刊：
影响因子：
4.5
通讯作者：
De Lay NR
中科院分区：
文献类型：
--
作者：
Cameron TA;Matz LM;De Lay NR
大约60年前，塞维罗·奥乔亚（Severo Ochoa）因发现多核苷酸磷酸化酶（PNDase）酶促合成RNA而获得诺贝尔生理学或医学奖。虽然这一发现为破译遗传密码提供了重要工具，但随后的工作表明，PNIPs在细菌和真核生物中的主要功能是催化逆反应，即，从RNA中释放核糖核苷酸。PNTR在细菌和真核生物中的RNA代谢中具有关键作用，主要通过其在加工和降解RNA中的作用，但最近报道了这种酶在RNA代谢中的其他功能。在这里，我们讨论了这些既定的和非经典的功能，PNDs和PNDs对细胞生理学的主要影响的可能性是通过其非正统的角色。多核苷酸磷酸化酶（polynucleotide phosphorylase，PNTR）广泛分布于细菌和真核生物中，是RNA代谢中的关键酶，在大多数生物体中作为3 - 5 bp的核糖核酸外切酶发挥作用。在细菌中，编码PNp 53的基因的失活导致广泛的后果，包括生长受损、应激反应减弱和毒力丧失。在哺乳动物中，PNTR在线粒体功能中具有重要作用。编码人类PNIPs（hPNIPs）的基因突变降低了其活性，可导致遗传性听力损失、脑肌病、严重轴突神经病、髓鞘形成延迟和Leigh综合征。在这篇综述中，我们强调了已报告的PNTR的典型和非正统的活动。具体来说，我们研究了它在细菌mRNA和rRNA衰变，RNA加工，小调控RNA（sRNA）降解和稳定中的作用。此外，我们探讨了最近报道的发现，在线粒体RNA的进口和降解和细胞质mRNA和非编码RNA衰变的hPNTAF的功能。尽管早在60多年前就被发现了，但我们仍然只是开始掌握PNTR的酶活性对细胞和生物生理学的贡献机制的广度。
Almost 60 years ago, Severo Ochoa was awarded the Nobel Prize in Physiology or Medicine for his discovery of the enzymatic synthesis of RNA by polynucleotide phosphorylase (PNPase). Although this discovery provided an important tool for deciphering the genetic code, subsequent work revealed that the predominant function of PNPase in bacteria and eukaryotes is catalyzing the reverse reaction, i.e., the release of ribonucleotides from RNA. PNPase has a crucial role in RNA metabolism in bacteria and eukaryotes mainly through its roles in processing and degrading RNAs, but additional functions in RNA metabolism have recently been reported for this enzyme. Here, we discuss these established and noncanonical functions for PNPase and the possibility that the major impact of PNPase on cell physiology is through its unorthodox roles. Widely distributed among bacteria and eukaryotes, including humans, polynucleotide phosphorylase (PNPase) is a critical enzyme in RNA metabolism that functions in most organisms as a 3ʹ to 5ʹ exoribonuclease. In bacteria, inactivation of the gene encoding PNPase results in a wide range of consequences, including impaired growth, diminished stress responses, and loss of virulence. In mammals, PNPase has an essential role in mitochondrial function. Mutations in the gene encoding the human PNPase (hPNPase) that reduce its activity can lead to hereditary hearing loss, encephalomyopathy, severe axonal neuropathy, delayed myelination, and Leigh syndrome. In this review, we highlight both the canonical and unorthodox activities that have been reported for PNPase. Specifically, we examine its role in bacterial mRNA and rRNA decay, RNA processing, and small regulatory RNA (sRNA) degradation and stabilization. Furthermore, we explore the recently reported findings on the function of hPNPase in mitochondrial RNA import and degradation and cytoplasmic mRNA and noncoding RNA decay. Despite being discovered more than six decades ago, we are still only beginning to grasp the breadth of mechanisms by which the enzymatic activities of PNPase contribute to cellular and organismal physiology.
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