Abstract
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.
Highlights
In a recent publication in Science, Wang et al found a long noncoding RNA expressed in human dendritic cells (DC), which they designated lnc-DC
The RNA interference (RNAi) interference with Wdnm1-like-ψ fragments resulted in a pronounced effect on Mo-DC differentiation as measured by expression of genes and molecules involved in the immune system, the ability to take up antigen, and the capacity to stimulate T-helper cells
The results and human model presented by Wang et al are generally convincing, yet some questions remain, such as to why not for all experiments both “no transfection control” and “control RNAi” were included, and why they only used a single RNAi control sequence
Summary
Correspondence In their recent publication in Science, Wang et al. aimed to identify lncRNAs involved in DC differentiation and function. Wang et al showed by a number of experiments that the Wdnm1-like-ψ transcript, in particular the 3’-end, has some specificity for binding to the STAT3 transcription factor and can reduce STAT3 dephosphorylation by phosphatase SHP1 Importantly, they showed that in their human Mo-DC differentiation model the effect of STAT3 inhibition caused similar effects as knockdown of Wdnm1-like-ψ. Within the serial analysis of gene expression (SAGE) experiment by Adachi et al., Wdnm1-like comprised the most abundant SAGE tag present exclusively in the limbal library, and the authors hypothesized that Wdnm1-like might be a marker of limbal stem cells They could, not rule out intron site (intron sequences not shown) coding part of Exon
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