Nucleolin is a Critical Regulator for Primary Transcripts of miR-31 to be a Peptide or an miRNA

A study to investigate the role of nucleolin in the regulation of pri-miR-31 to be a peptide or an miRNA. During the activation of CD4+ T cells, the localization of pri-miR-31 shifts from cytoplasm into nucleus, consistent with increasing miR-31 expression and reduced miPEP31, the encoded product of pri-miR-31. We identified nucleolin as the regulator of pri-miR-31. The RNA binding domain of nucleolin interacts with pri-miR-31 through recognizing a G-quadruplex structure. Furthermore, nucleolin binds to a subset of G-quadruplex containing pri-miRNAs, subsequently regulating metabolic reprogramming and activation of CD4+ T cells. After screening endogenous RNA aptamers targeting nucleolin, we found that rG215 relieves the development of experimental colitis via inhibiting the pathogenic CD4+ T cells. Collectively, our results identified nucleolin as a critical regulator of the fate determination of pri-miRNAs and provided a new potential strategy to treat autoimmune diseases.