A Kinase and a Glycosylase Catabolize Pseudouridine in the Peroxisome to Prevent Toxic Pseudouridine Monophosphate Accumulation
A Kinase and a Glycosylase Catabolize Pseudouridine in the Peroxisome to Prevent Toxic Pseudouridine Monophosphate Accumulation
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激酶和糖基酶分解过氧化物酶体中的假尿苷，以防止有毒的单磷酸假尿苷积累
DOI：
10.1105/tpc.19.00639
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发表时间：
2020-03-01
期刊：
影响因子：
11.6
通讯作者：
Witte, Claus-Peter
中科院分区：
文献类型：
--
作者：
Chen, Mingjia;Witte, Claus-Peter
假尿苷（Pseudouridine，psi）是非编码RNA和mRNA中常见的核苷修饰，在拟南芥过氧化物酶体中被降解以防止毒性中间产物假尿苷一磷酸的积累。在假尿苷中，尿嘧啶的C5通过不寻常的C-糖苷键连接到Rib上。这种RNA修饰是通过尿苷（U）的位点特异性转糖基化（一种由假尿苷脱氢酶介导的过程）引入RNA的。RNA不断更新，释放游离的假尿苷，但假尿苷在真核生物中的代谢命运尚不清楚。在这里，我们表明在拟南芥（Arabidopsis thaliana）中，假尿苷在过氧化物酶体中被（1）来自PfkB家族的假尿苷激酶（PUKI）分解代谢，产生5 '-假尿苷单磷酸（5 '-psi MP），和（2）psi MP糖基化酶（PsiMP）将psi MP水解为尿嘧啶和核糖-5-磷酸.损害假尿苷催化剂导致强假尿苷积累和增加的psi MP含量。psi MP是有毒的，导致延迟的发芽和生长抑制，但损害假尿苷催化剂不影响RNA中的psi/U比率。二分过氧化物酶体PUKI和PUKI Y在植物和藻类中是保守的，而一些真菌和大多数动物（哺乳动物除外）可能在线粒体中拥有PUKI-PUKI融合蛋白。我们认为核糖体RNA的液泡周转通过3 '-psi MP产生大部分的假尿苷池，其通过胞质溶胶输入到过氧化物酶体中，用于由PUKI和PUKI Y降解，这是一个涉及有毒的5 '-psi MP中间体的过程。
Pseudouridine, a frequent nucleoside modification in noncoding RNA and mRNA, is degraded in Arabidopsis peroxisomes to prevent the accumulation of the toxic intermediate pseudouridine monophosphate.Pseudouridine (psi) is a frequent nucleoside modification that occurs in both noncoding RNAs and mRNAs. In pseudouridine, C5 of uracil is attached to the Rib via an unusual C-glycosidic bond. This RNA modification is introduced on the RNA by site-specific transglycosylation of uridine (U), a process mediated by pseudouridine synthases. RNA is subject to constant turnover, releasing free pseudouridine, but the metabolic fate of pseudouridine in eukaryotes is unclear. Here, we show that in Arabidopsis (Arabidopsis thaliana), pseudouridine is catabolized in the peroxisome by (1) a pseudouridine kinase (PUKI) from the PfkB family that generates 5 '-pseudouridine monophosphate (5 '-psi MP) and (2) a psi MP glycosylase (PUMY) that hydrolyzes psi MP to uracil and ribose-5-phosphate. Compromising pseudouridine catabolism leads to strong pseudouridine accumulation and increased psi MP content. psi MP is toxic, causing delayed germination and growth inhibition, but compromising pseudouridine catabolism does not affect the psi/U ratios in RNA. The bipartite peroxisomal PUKI and PUMY are conserved in plants and algae, whereas some fungi and most animals (except mammals) possess a PUMY-PUKI fusion protein, likely in mitochondria. We propose that vacuolar turnover of ribosomal RNA produces most of the pseudouridine pool via 3 '-psi MP, which is imported through the cytosol into the peroxisomes for degradation by PUKI and PUMY, a process involving a toxic 5 '-psi MP intermediate.