title: lncRHOXF1, a Long Noncoding RNA from the X Chromosome That Suppresses Viral Response Genes during Development of the Early Human Placenta.
abstract: 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 that is 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 small interfering RNAs (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.
authors.affiliation: Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Ian
authors.initials: I
authors.lastname: Penkala
authors.affiliation: Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Jianle
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Camille M
authors.initials: CM
authors.lastname: Syrett
authors.affiliation: Department of Obstetrics and Gynecology, Shriners Hospitals Pediatric Research Center, Center for Neural Repair and Rehabilitation, Temple University, Philadelphia, Pennsylvania, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Goetzl
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Carolina B
authors.initials: CB
authors.lastname: López
authors.affiliation: Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA anguera@vet.upenn.edu.
authors.forename: Montserrat C
authors.initials: MC
authors.lastname: Anguera
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000235:genetics; D049109:Cell Proliferation; D002877:Chromosomes, Human / Q000235:genetics*; D003593:Cytoplasm / Q000235:genetics; D005260:Female; D000066449:Human Embryonic Stem Cells / Q000166:cytology*; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D051379:Mice; D010929:Placentation; D026723:Polyadenylation; D011247:Pregnancy; D062085:RNA, Long Noncoding / Q000235:genetics*; D010253:Respirovirus Infections / Q000276:immunology*; D029082:Sendai virus / Q000502:physiology; D014327:Trophoblasts / Q000166:cytology / Q000276:immunology / Q000821:virology
chemical_list: D007370:Interferon Type I; D062085:RNA, Long Noncoding; C000619242:long non-coding RNA RHOXF1, human