Conjunction of potential G-quadruplex and adjacent cis-elements in the 5' UTR of hepatocyte nuclear factor 4-alpha strongly inhibit protein expression.

ABSTRACT: Hepatocyte nuclear factor 4-alpha (HNF4α) is a well established master regulator of liver development and function. We identified the in vitro presence of a stable secondary structure, G-quadruplex (G4) in the 5' UTR of P1-HNF4A, the predominant HNF4α isoform(s) in adult liver. Our data suggest that the cooperation of G4 and the adjacent putative protein-binding sites within the 5' UTR was necessary and sufficient to mediate a strong translational repression. This was supported by analysis of deleted/mutated 5'UTRs and two native regulatory single-nucleotide polymorphisms in the 5'UTR. Additional results indicated that G4 motifs in the 5' UTRs of other liver-enriched transcription factors also inhibited protein expression. Moreover, pyridostatin, a G4 ligand, specifically potentiated the t

SUBMITTER: Guo S 

PROVIDER: S-EPMC5727235 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature