Dijkstra Johannes M, Ballingall Keith T
Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, 470-1192, Japan.
Moredun Research Institute, Penicuik, Midlothian, Scotland, EH26 0PZ, UK.
F1000Res. 2014 Jul 11;3:160. doi: 10.12688/f1000research.4711.2. eCollection 2014.
In a recent publication in Science, Wang et al. found a long noncoding RNA (lncRNA) expressed in human dendritic cells (DC), which they designated lnc-DC. Based on lentivirus-mediated RNA interference (RNAi) experiments in human and murine systems, they concluded that lnc-DC is important in differentiation of monocytes into DC. However, Wang et al. did not mention that their so-called "mouse lnc-DC ortholog" gene was already designated " Wdnm1-like" and is known to encode a small secreted protein. We found that incapacitation of the Wdnm1-like open reading frame (ORF) is very rare among mammals, with all investigated primates except for hominids having an intact ORF. The null-hypothesis by Wang et al. therefore should have been that the human lnc-DC transcript might only represent a non-functional relatively young evolutionary remnant of a protein coding locus. Whether this null-hypothesis can be rejected by the experimental data presented by Wang et al. depends in part on the possible off-target (immunogenic or otherwise) effects of their RNAi procedures, which were not exhaustive in regard to the number of analyzed RNAi sequences and control sequences. If, however, the conclusions by Wang et al. on their human model are correct, and they may be, current knowledge regarding the Wdnm1-like locus suggests an intriguing combination of different functions mediated by transcript and protein in the maturation of several cell types at some point in evolution. We feel that the article by Wang et al. tends to be misleading without the discussion presented here.
在最近发表于《科学》杂志的一篇论文中，王等人发现了一种在人类树突状细胞（DC）中表达的长链非编码RNA（lncRNA），他们将其命名为lnc-DC。基于在人类和小鼠系统中进行的慢病毒介导的RNA干扰（RNAi）实验，他们得出结论，lnc-DC在单核细胞分化为DC的过程中起重要作用。然而，王等人没有提到他们所谓的“小鼠lnc-DC直系同源基因”已被命名为“Wdnm1-like”，并且已知该基因编码一种小的分泌蛋白。我们发现，Wdnm1-like开放阅读框（ORF）失活在哺乳动物中非常罕见，除了人科动物外，所有被研究的灵长类动物都有完整的ORF。因此，王等人的零假设应该是，人类lnc-DC转录本可能只是一个蛋白质编码基因座的无功能的相对年轻的进化残余物。王等人所展示的实验数据是否能够推翻这个零假设，部分取决于他们RNAi程序可能存在的脱靶（免疫原性或其他）效应，而他们在分析的RNAi序列和对照序列数量方面并不详尽。然而，如果王等人关于其人类模型的结论是正确的，而且有可能是正确的，那么目前关于Wdnm1-like基因座的知识表明，在进化的某个阶段，转录本和蛋白质在几种细胞类型成熟过程中介导了不同功能的有趣组合。我们认为，如果没有此处所呈现的讨论，王等人的文章往往会产生误导。
