Landscape of the complete RNA chemical modifications in the human 80S ribosome.
Landscape of the complete RNA chemical modifications in the human 80S ribosome.
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DOI：
10.1093/nar/gky811
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发表时间：
2018-10-12
影响因子：
14.9
通讯作者：
Isobe T
中科院分区：
文献类型：
--
作者：
Taoka M;Nobe Y;Yamaki Y;Sato K;Ishikawa H;Izumikawa K;Yamauchi Y;Hirota K;Nakayama H;Takahashi N;Isobe T
在核糖体生物发生期间，核糖体RNA获得确保翻译保真度的各种化学修饰，并且修饰过程的失调可引起蛋白质组变化，如在癌症和遗传性人类疾病中观察到的。在这里，我们报告了完整的化学修饰的所有RNA的人80 S核糖体的定量质谱测定。我们分配了228个位点，其中有14个不同的转录后修饰，其中大部分位于核糖体的功能区域。检测到的所有修饰都是典型的真核核糖体RNA，并且没有观察到人类特异性修饰，与最近报道的冷冻电子显微镜分析相反。虽然人类核糖体RNA似乎有很少的多态性的转录后修饰，我们发现，在28 S核糖体RNA的两个特定位点的假尿苷化显着减少，在核糖体的家族性先天性角化不良，一种遗传性疾病引起的点突变，在假尿苷合酶基因DKC 1。整个表转录组核糖体RNA修饰的景观为理解与人类疾病相关的核糖体功能和功能障碍提供了坚实的基础。
During ribosome biogenesis, ribosomal RNAs acquire various chemical modifications that ensure the fidelity of translation, and dysregulation of the modification processes can cause proteome changes as observed in cancer and inherited human disorders. Here, we report the complete chemical modifications of all RNAs of the human 80S ribosome as determined with quantitative mass spectrometry. We assigned 228 sites with 14 different post-transcriptional modifications, most of which are located in functional regions of the ribosome. All modifications detected are typical of eukaryotic ribosomal RNAs, and no human-specific modifications were observed, in contrast to a recently reported cryo-electron microscopy analysis. While human ribosomal RNAs appeared to have little polymorphism regarding the post-transcriptional modifications, we found that pseudouridylation at two specific sites in 28S ribosomal RNA are significantly reduced in ribosomes of patients with familial dyskeratosis congenita, a genetic disease caused by a point mutation in the pseudouridine synthase gene DKC1. The landscape of the entire epitranscriptomic ribosomal RNA modifications provides a firm basis for understanding ribosome function and dysfunction associated with human disease.
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在人rRNA中2'-O-ME的分析揭示了一部分部分修饰的位置，并提供了核糖体异质性的证据。
影响因子：
14.9
作者：
Krogh N;Jansson MD;Häfner SJ;Tehler D;Birkedal U;Christensen-Dalsgaard M;Lund AH;Nielsen H
通讯作者：
Nielsen H
影响因子：
14.9
作者：
Incarnato D;Anselmi F;Morandi E;Neri F;Maldotti M;Rapelli S;Parlato C;Basile G;Oliviero S
通讯作者：
Oliviero S
影响因子：
9.8
作者：
Li Z;Lee I;Moradi E;Hung NJ;Johnson AW;Marcotte EM
通讯作者：
Marcotte EM
影响因子：
64.8
作者：
Jeong, H;Mason, SP;Oltvai, ZN
通讯作者：
Oltvai, ZN
影响因子：
5.6
作者：
MADEN, BEH;SALIM, M
通讯作者：
SALIM, M