Makarova Julia A, Kramerov Dmitri A
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
Gene. 2005 Dec 19;363:51-60. doi: 10.1016/j.gene.2005.08.010. Epub 2005 Oct 14.
Non-coding RNAs are involved in many cellular processes. In particular, most of C/D box small nucleolar RNAs (snoRNAs) function as guide RNAs in site-specific 2'-O-methylation of rRNAs. While most snoRNA genes reside in introns of protein-coding genes, here we demonstrated an unusual snoRNA gene occupying an intron of a previously unknown non-protein-coding gene U87HG. We characterized this host gene in human, mouse, rat, and dog. It is a member of 5'TOP gene family, which includes many translation apparatus genes. U87HG RNA carried multiple stop-codons and was associated with ribosomes, suggesting that it may be a target for nonsense-mediated mRNA decay (NMD), a process that eliminates transcripts bearing nonsense mutations. Surprisingly, we found that U87HG RNA was hardly susceptible to NMD. Possible mechanisms (translation reinitiation, ribosomal leaky scanning, and low efficiency of translation) of this phenomenon are discussed. Unlike transcripts of four other known non-protein-coding host genes, U87HG RNA shows a relatively high degree of conservation suggesting a selective pressure and a possible functional activity of U87HG apart from producing U87 snoRNA.
非编码RNA参与许多细胞过程。特别是,大多数C/D盒小核仁RNA(snoRNA)在rRNA的位点特异性2'-O-甲基化中作为引导RNA发挥作用。虽然大多数snoRNA基因位于蛋白质编码基因的内含子中,但在此我们展示了一个不寻常的snoRNA基因,它占据了一个先前未知的非蛋白质编码基因U87HG的内含子。我们在人、小鼠、大鼠和狗中对这个宿主基因进行了表征。它是5'TOP基因家族的成员,该家族包括许多翻译装置基因。U87HG RNA携带多个终止密码子并与核糖体相关联,这表明它可能是无义介导的mRNA降解(NMD)的靶标,NMD是一个消除带有无义突变转录本的过程。令人惊讶的是,我们发现U87HG RNA几乎不易受到NMD的影响。本文讨论了这种现象可能的机制(翻译重新起始、核糖体渗漏扫描和翻译效率低下)。与其他四个已知的非蛋白质编码宿主基因的转录本不同,U87HG RNA显示出相对较高的保守程度,这表明存在选择压力以及U87HG除了产生U87 snoRNA之外可能具有的功能活性。