Endogenous miRNAs posttranscriptionally regulate virtually every

Endogenous miRNAs posttranscriptionally regulate virtually every cellular process,[4]

so it is not surprising that viruses modulate the host miRNA milieu in different ways to facilitate pathogenesis.[5] Herein, we have shown that a liver-abundant miRNA, miR-27, is robustly induced by HCV in both in vitro and in vivo models (Figs. 1, 5), and this modulation is conserved across at least two genotypes (Figs. 1, 2, 5). HCV-induced expression of miR-27b requires replication of the virus while viral translation is sufficient to activate miR-27a expression (Fig. 1C,D), suggesting these isoforms are modulated by HCV through different mechanisms. In order to understand HCV’s induction of miR-27, we studied its effects on hepatocytes. Overexpression of either isoform of miR-27 causes an accumulation of hepatic lipid content in the presence or absence of

HCV (Figs. 2, 5). The correlation between miR-27 expression and cellular lipid content was also observed in HCV-infected VX-809 solubility dmso SCID-beige/Alb-uPa mice (Fig. 5C). This represents, to the best of our knowledge, the first report visualizing HCV-induced hepatic lipid accumulation in SCID-beige/Alb-uPa mice, highlighting the model’s utility for studying HCV-associated steatosis. Together, these data demonstrate that the up-regulation of miR-27 by HCV contributes to increased lipid accumulation and larger LDs. Accumulation of hepatic LDs correlates with increased expression of miR-27 whose predicted target genes are associated with lipid metabolism (PPAR-α and ANGPTL3) (Supporting Fig. S4A). Targetscan predicts that PPAR-α mRNA possesses two miR-27 binding sites in its INK 128 concentration 3′-UTR, the region generally targeted by microRNAs (Supporting Fig. S7). Previous work suggested that miR-27b regulates PPAR-α largely at the translational level.[29] Our results suggest a direct interaction between miR-27b and PPAR-α mRNA; however, Kida et al.[29] were not able to confirm a functional

interaction in their predicted miR-27 binding sites of PPAR-α. Our observation of decreased PPAR-α mRNA during miR-27b overexpression strongly suggests a miR-27-induced effect at the mRNA level as this website well, and may reflect differences in cells, in transfection efficiency, and in potency of mimics. ANGPTL3 harbors a poorly conserved miR-27 binding site in the 3′-UTR and a highly conserved open reading frame (ORF) site (Supporting Fig. S7) predicted to be functional, as it is preceded by rare codons (Supporting Fig. S7).[14] These rare codons can cause ribosomal pausing and allow stable interactions between miR-27 and the binding site.[36] Our results suggest that miR-27b regulates ANGPTL3 at the RNA level, consistent with previous results.[14] PPAR-α heterodimerizes with RXR-α to transcriptionally activate genes associated with fatty acid β-oxidation.[30] Our data shows that HCV inhibits the PPAR-α pathway through enhancement of miR-27-mediated repression of PPAR-α expression that also leads to TG accumulation.

Related posts:

  1. 8 The discovery of miRNAs is one of the major developments in mol
  2. The three higher affinity ligands immediately regulate cyclin D1
  3. TGFB and KLF6 cooperatively regulate a broad array of cellular pr
  4. APPL1 and Akt regulate cell migration and adhesion dynamics Consi
  5. To better define the effect of endogenous transactivation of PPAR
This entry was posted in Antibody. Bookmark the permalink.

Leave a Reply

Your email address will not be published. Required fields are marked *

*

You may use these HTML tags and attributes: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <strike> <strong>