Poly(rC) binding protein 2 acts as a negative regulator of IRES-mediated translation of Hr mRNA

During the hair follicle (HF) cycle, HR protein expression is not concordant with the presence of the Hr mRNA transcript, suggesting an elaborate regulation of Hr gene expression. Here we present evidence that the 5' untranslated region (UTR) of the Hr gene has internal ribosome entry site (IRES) activity and this activity is regulated by the binding of poly (rC) binding protein 2 (PCBP2) to Hr mRNA. Overexpression and knockdown of PCBP2 resulted in a decrease in Hr 5' UTR IRES activity and an increase in HR protein expression without changing mRNA levels. We also found that this regulation was disrupted in a mutant Hr 5' UTR that has a mutation responsible for Marie Unna hereditary hypotrichosis (MUHH) in both mice and humans. These findings suggest that Hr mRNA expression is regulated at the post-transcriptional level via IRES-mediated translation control through interaction with PCPB2, but not in MUHH.