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Ultraconserved (uc) RNAs, a class of long non-coding RNAs (lncRNAs), are conserved across humans, mice, and rats, but the physiological significance and pathological role of ucRNAs is largely unknown. Here we show that uc.372 is upregulated in the livers of db/db mice, HFD-fed mice, and NAFLD patients. Gain-of-function and loss-of-function studies indicate that uc.372 drives hepatic lipid accumulation in mice by promoting lipogenesis. We further demonstrate that uc.372 binds to pri-miR-195/pri-miR-4668 and suppresses maturation of miR-195/miR-4668 to regulate expression of genes related to lipid synthesis and uptake, including ACC, FAS, SCD1, and CD36. Finally, we identify that uc.372 is located downstream of the insulinoma-associated 2 (INSM2) gene that is transcriptionally activated by upstream transcription factor 1 (USF1). Our findings reveal a novel mechanism by which uc.372 drives hepatic steatosis through inhibition of miR-195/miR-4668 maturation to relieve miR-195/miR-4668-mediated suppression of functional target gene expression.
Pubmed ID: 29426937 RIS Download
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View all literature mentionsIn an effort to strongly support the collaborative nature of scientific research, BIOBASE offers academic and non-profit organizations free access to reduced functionality versions of their products. TRANSFAC Professional provides gene regulation analysis solutions, offering the most comprehensive collection of eukaryotic gene regulation data. The professional paid subscription gives customers access to up-to-date data and tools not available in the free version. The public databases currently available for academic and non-profit organizations are: * TRANSFAC: contains data on transcription factors, their experimentally-proven binding sites, and regulated genes. Its broad compilation of binding sites allows the derivation of positional weight matrices. * TRANSPATH: provides data about molecules participating in signal transduction pathways and the reactions they are involved in, resulting in a complex network of interconnected signaling components.TRANSPATH focuses on signaling cascades that change the activities of transcription factors and thus alter the gene expression profile of a given cell. * PathoDB: is a database on pathologically relevant mutated forms of transcription factors and their binding sites. It comprises numerous cases of defective transcription factors or mutated transcription factor binding sites, which are known to cause pathological defects. * S/MARt DB: presents data on scaffold or matrix attached regions (S/MARs) of eukaryotic genomes, as well as about the proteins that bind to them. S/MARs organize the chromatin in the form of functionally independent loop domains gained increasing support. Scaffold or Matrix Attached Regions (S/MARs) are genomic DNA sequences through which the chromatin is tightly attached to the proteinaceous scaffold of the nucleus. * TRANSCompel: is a database on composite regulatory elements affecting gene transcription in eukaryotes. Composite regulatory elements consist of two closely situated binding sites for distinct transcription factors, and provide cross-coupling of different signaling pathways. * PathoSign Public: is a database which collects information about defective cell signaling molecules causing human diseases. While constituting a useful data repository in itself, PathoSign is also aimed at being a foundational part of a platform for modeling human disease processes.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsCell line Hep-G2 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
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