Shlnc-EC6 regulates murine erythroid enucleation by Rac1-PIP5K pathway.

Long noncoding RNAs (LncRNAs) are longer than 200 nucleotide noncoding RNAs without apparent functional coding capacity that function as regulators of cell growth and development. In recent years, increasing evidence implicates the involvement of LncRNAs in erythropoiesis. shlnc-EC6 is a LncRNA associated with erythroid differentiation but the mechanism remains undefined. In this study, we found that knockdown of shlnc-EC6 in purified mouse fetal liver erythroid progenitor and hematopoietic stem cells (FLEPHSCs) significantly blocked erythroid enucleation. We also showed that Rac1 was negatively regulated by shlnc-EC6 at the posttranscriptional level via specific binding to sites within the 3'UTR of Rac1 mRNA. Moreover, we found that knockdown of shlnc-EC6 led to upregulation of Rac1, followed by the activation of the downstream protein PIP5K, and subsequently resulted in the inhibition of enucleation in cultured mouse fetal erythroblasts. Thus, our findings suggest that shlnc-EC6 acts as a novel modulator to regulate mouse erythropoiesis via Rac1/PIP5K signaling pathway.