Project description:The nuclear receptor, Farnesoid X Receptor (FXR, NR1H4), is a key transcriptional regulator of metabolism and a promising drug target for non-alcoholic fatty liver disease (NAFLD), a leading cause of liver failure and death. Protein coding genes regulated by FXR are known, but it remains unknown whether FXR mediates its function through regulating expression of long non-coding RNA (lncRNA) genes. Utilizing global RNA-seq and Gro-seq analyses, we identify an FXR-induced novel long non-coding RNA (lncRNA), termed FincoR.
Project description:Long non-coding RNAs (lncRNAs) are important regulators of the immune response. Here we identify a novel function for the primate-specific lncRNA, CHROMR. We established that CHROME is most highly transcribed in human macrophages treated with influenza virus and/or polyIC.
Project description:Long non-coding RNAs (lncRNAs) are important regulators of the immune response. Here we identify a novel function for the primate-specific lncRNA, CHROME. We established that CHROME is most highly transcribed in human macrophages treated with influenza virus and/or polyIC.
Project description:Long non-coding RNAs (lncRNAs) are important regulators of the immune response. Here we identify a novel function for the primate-specific lncRNA, CHROME. We established that CHROME is most highly transcribed in human macrophages treated with bacterial lipopolysaccharide and RNA viruses.
Project description:Long non-coding RNAs (lncRNAs) are important regulators of the immune response. Here we identify a novel function for the primate-specific lncRNA, CHROME. We established that CHROME is most highly transcribed in human macrophages treated with influenza virus and/or polyIC.
Project description:Long non-coding RNAs (lncRNAs) are important regulators of the immune response. Here we identify a novel function for the primate-specific lncRNA, CHROME. We established that CHROME is most highly transcribed in human macrophages treated with bacterial lipopolysaccharide and RNA viruses.
Project description:Prenatal cadmium (Cd) exposure leads to immunotoxic phenotypes in the offspring. Long non-coding RNAs (lncRNAs) are integral to T cell regulation. Here, we identified genes and pathways altered in CD4+ T cell by prenatal Cd exposure. We investigated the role of long non-coding RNA small nucleolar RNA hostgene 7 (lncSnhg7) in T cell proliferation: LncSnhg7 expression increases in CD4+ T cells following stimulation with anti-CD3/CD28 beads. LngSnhg7 and a downstream protein, GALNT7, are upregulated in T cells from offspring exposed to Cd during gestation. Overexpression of miR-34a, a regulator of lnhcSnhg7 and GALNT7, suppresses GALNT7 protein levels in primary T cells, but not in a mouse T lymphocyte cell line. The T cells isolated from Cd-exposed offspring exhibit increased proliferation after activation in vitro, but Treg suppression and CD4+ T cell apoptosis are not affected by prenatal Cd exposure. In conclusion, prenatal Cd exposure alters the expression of lncRNAs during T cell activation. The induction of lncSnhg7 is enhanced in splenic T cells from Cd offspring resulting in the upregulation of GALNT7 protein and increased proliferation following activation. miR-34a overexpression decreased GALNT7 expression suggesting that the lncSnhg7/miR-34a/GALNT7 is an important pathway in primary CD4+ T cells. These data highlight the need to understand the consequences of environmental exposures on lncRNA functions in non-cancerous cells.
Project description:LncRNAs are involved in critical processes for cell homeostasis and function. However, it remains largely unknown whether and how the transcriptional regulation of long noncoding RNAs results in activity-dependent changes at the synapse and facilitate formation of long-term memories. Here, we report the identification of a novel lncRNA, SLAMR, that becomes enriched in CA1- but not in CA3-hippocampal neurons upon contextual fear conditioning. SLAMR is transported to dendrites via the molecular motor KIF5C and recruited to the synapse in response to stimulation. Loss of function of SLAMR reduced dendritic complexity and impaired activity-dependent changes in spine structural plasticity. Interestingly, the gain of function of SLAMR enhanced dendritic complexity, and spine density through enhanced translation. Analyses of the SLAMR interactome revealed its association with CaMKIIa protein through a 220-nucleotide element and its modulation of CaMKIIa activity. Furthermore, loss-of-function of SLAMR in CA1 selectively impairs consolidation but neither acquisition, recall, nor extinction of fear memory and spatial memory. Together, these results establish a new mechanism for activity dependent changes at the synapse and consolidation of contextual fear memory.
