LNCRHOXF1: a long noncoding RNA from the X-chromosome that suppresses viral response genes during development of the early human placenta

Long noncoding RNAs (lncRNAs) can regulate gene expression in a cell-specific fashion during development. Here we identify a novel lncRNA from the X-chromosome that we named lncRHOXF1 and which is abundantly expressed in trophectoderm and primitive endoderm cells of human blastocyst-stage embryos. LncRHOXF1 is a spliced and polyadenylated lncRNA about 1 kb in length, found in both the nuclear and cytoplasmic compartments of in vitro differentiated human trophectoderm progenitor cells. Gain of function experiments in human embryonic stem cells, which normally lack lncRHOXF1 RNA, revealed that lncRHOXF1 reduced proliferation and favored cellular differentiation. LncRHOXF1 knockdown using siRNAs in human trophectoderm progenitors increased expression of viral response genes, including type I interferon. Sendai virus infection of human trophectoderm progenitor cells increased lncRHOXF1 RNA levels and siRNA-mediated disruption of lncRHOXF1 during infection reduced the expression of viral response genes leading to higher virus replication. Thus, lncRHOXF1 RNA is the first example of a lncRNA that regulates the host response to viral infections in human placental progenitor cells, and we propose that it functions as a repressor of the viral response during early human development. Undifferentiated human embryonic stem cells (HUES9) containing the lncRHOXF1 and rtTA3 cDNAs inserted into the AAVS locus of chromosome 19 were used in overexpression experiments RNA was isolated from triplicate wells for analysis by Illumina microarray.