Making Sense of Antisense: Seemingly Noncoding RNAs Antisense to the Master Regulator of Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication Do Not Regulate That Transcript but Serve as mRNAs Encoding Small Peptides
Making Sense of Antisense: Seemingly Noncoding RNAs Antisense to the Master Regulator of Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication Do Not Regulate That Transcript but Serve as mRNAs Encoding Small Peptides
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DOI：
10.1128/jvi.02705-09
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发表时间：
2010-06-01
影响因子：
5.4
通讯作者：
Ganem, Don
中科院分区：
文献类型：
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作者：
Xu, Yiyang;Ganem, Don
哺乳动物的转录组中充满了推定的非编码RNA，其中许多是已知的开放阅读框（ORF）的反义。调节其互补mRNA的作用通常被归因于这些反义转录本，但很少有人经过实验研究，而且这些功能在很大程度上仍然是猜测。卡波西肉瘤相关疱疹病毒（KSHV）编码两个转录本，缺乏明显的ORF，并与编码潜伏/裂解开关的主调节因子的基因（RTA）互补。在这里，我们表明，与预期相反，这些RNA不调节RTA表达。相反，它们在多核糖体上被发现，遗传分析表明，翻译起始发生在RNA中的几个AUG密码子处，导致推测合成17至48个氨基酸的肽。这些发现强调了在编码潜力的计算评估中需要谨慎，并提出了哺乳动物蛋白质组可能包含许多先前未被怀疑的由看似非编码RNA产生的肽的可能性，其中一些可能具有重要的生物学功能。不管它们的功能如何，这些肽也可以对未感染和感染细胞中产生的T细胞表位库有实质性贡献。
The mammalian transcriptome is studded with putative noncoding RNAs, many of which are antisense to known open reading frames (ORFs). Roles in the regulation of their complementary mRNAs are often imputed to these antisense transcripts, but few have been experimentally examined, and such functions remain largely conjectural. Kaposi's sarcoma-associated herpesvirus (KSHV) encodes two transcripts that lack obvious ORFs and are complementary to the gene (RTA) encoding the master regulator of the latent/lytic switch. Here, we show that, contrary to expectation, these RNAs do not regulate RTA expression. Rather, they are found on polysomes, and genetic analysis indicates that translational initiation occurs at several AUG codons in the RNA, leading to the presumptive synthesis of peptides of 17 to 48 amino acids. These findings underscore the need for circumspection in the computational assessment of coding potential and raise the possibility that the mammalian proteome may contain many previously unsuspected peptides generated from seemingly noncoding RNAs, some of which could have important biological functions. Irrespective of their function, such peptides could also contribute substantially to the repertoire of T cell epitopes generated in both uninfected and infected cells.