Abstract

Messenger RNA (mRNA) decay utilizes both exoribonucleolytic and endoribonucleolytic enzymes where the latter are generally more prone to be transcript-specific. An erythroid-enriched endoribonuclease, ErEN, can destabilize the α -globin mRNA through directing a site-specific cleavage within the 3 untranslated region (3 UTR) both in vitro and in vivo. ErEN activity is sequence- and/or local structure-specific as the minimal recognition/cleavage sequence can be conferred onto a heterologous RNA and mutations at the cleavage site immunize the mRNA from ErEN hydrolysis. Interestingly, the ErEN cleavage activity is regulated by an mRNA stability complex (α -complex). An interaction between the α -complex and the poly(A)-binding protein (PABP) accentuates α -complex binding to a region overlapping the ErEN cleavage site and further prevents premature ErEN-mediated decay. At present the identity of ErEN remains elusive, yet its identification will provide mechanistic and functional insights into the general processes of endoribonuclease-mediated mRNA turnover and erythropoiesis.

Keywords: α-globin, endoribonuclease, ErEN, erythropoiesis, mRNA decay