Deficiency of Antisense lncRNA Gm48853 Resulted in Embryonic Lethality and Impaired Placental Development in Mice

Objective:Long noncoding RNAs(lncRNAs)play important roles in embryonic development and in various diseases.Gm48853 is a predicted natural antisense lncRNA gene of unknown function.The present study aimed to investigate its expression and function.Methods:Quantitative reverse transcription-polymerase chain reaction and sequencing were used to detect the expression of Gm48853 antisense lncRNA.Hematoxylin and eosin staining and pathological analysis were applied to evaluate the effects of Gm48853 mutations on embryonic/placental development.5-Ethynyl-2’-deoxyuridine(EdU)and terminal deoxynucleotidyl transferase deoxy-UTP-nick-end labeling assays were used to analyze the status of cell proliferation and apoptosis in Gm48853-deficient embryos and placentas.Results:PiggyBac(PB)transposon insertion into the intron of Gm48853 resulted in a significant decrease in Gm48853 expression and embryonic lethality at midgestation.Homozygous Gm48853 mutations led to severe growth retardation of embryos and impaired the morphogenesis of the placental labyrinth.In addition,cell proliferation was dramatically decreased in Gm48853^(PB/PB) embryos and placentas,and apoptosis was radically increased in the mutant embryos but not in the mutant placentas.Conclusion:Antisense lncRNA Gm48853 may regulate embryonic/placental development by enhancing cell proliferation and/or inhibiting apoptosis.

What do we know about the role of lncRNAs in multiple sclerosis?

Multiple sclerosis is a chronic, inflammatory and degenerative disease of the central nervous system of unknown aetiology although well-defined evidence supports an autoimmune pathogenesis. So far, the exact mechanisms leading to autoimmune diseases are still only partially understood. We know that genetic, epigenetic, molecular, and cellular factors resulting in pathogenic inflammatory responses are certainly involved. Long non-coding RNAs(lncRNAs) are non-protein coding transcripts longer than 200 nucleotides that play an important role in both innate and acquired immunity, so there is great interest in lncRNAs involved in autoimmune diseases. The research on multiple sclerosis has been enriched with many studies on the molecular role of lncRNAs in the pathogenesis of the disease and their potential application as diagnostic and prognostic biomarkers. In particular, many multiple sclerosis fields of research are based on the identification of lncRNAs as possible biomarkers able to predict the onset of the disease, its activity degree, its progression phase and the response to disease-modifying drugs. Last but not least, studies on lncRNAs can provide a new molecular target for new therapies, missing, so far, a cure for multiple sclerosis. While our knowledge on the role of lncRNA in multiple sclerosis has recently improved, further studies are required to better understand the specific role of lncRNAs in this neurological disease. In this review, we present the most recent studies on molecular characterization of lncRNAs in multiple sclerosis disorder discussing their clinical relevance as biomarkers for diagnosis and treatments.