title: Cooperative interplay of let-7 mimic and HuR with MYC RNA.
abstract: Both RNA-binding proteins (RBP) and miRNA play important roles in the regulation of mRNA expression, often acting together to regulate a target mRNA. In some cases the RBP and miRNA have been reported to act competitively, but in other instances they function cooperatively. Here, we investigated HuR function as an enhancer of let-7-mediated translational repression of c-Myc despite the separation of their binding sites. Using an in vitro system, we determined that a let-7 mimic, consisting of single-stranded (ss)DNA complementary to the let-7 binding site, enhanced the affinity of HuR for a 122-nt MYC RNA encompassing both binding sites. This finding supports the biophysical principle of cooperative binding by an RBP and miRNA purely through interactions at distal mRNA binding sites.
authors.affiliation: a Biochemistry and Molecular Biology; Monash University ; Melbourne , VIC Australia.
authors.forename: Menachem J
authors.initials: MJ
authors.lastname: Gunzburg
authors.forename: Andrew
authors.initials: A
authors.lastname: Sivakumaran
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Pendini
authors.forename: Je-Hyun
authors.initials: JH
authors.lastname: Yoon
authors.forename: Myriam
authors.initials: M
authors.lastname: Gorospe
authors.forename: Matthew C J
authors.initials: MC
authors.lastname: Wilce
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Wilce
mesh_terms: D000067780:ELAV-Like Protein 1 / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000378:metabolism*; D018716:Molecular Mimicry / Q000502:physiology*; D011485:Protein Binding / Q000502:physiology; D016271:Proto-Oncogene Proteins c-myc / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc; C487931:mirnlet7 microRNA, human
keywords: 3′-UTR; HuR; RNA-binding protein (RBP); c-Myc; cooperative binding; let-7; mRNA; miRNA; surface plasmon resonance (SPR); translational repression