MED19-CLIP-seq
The Mediator complex is an essential regulator of Pol II-dependent transcription, and MED19 is a subunit of this complex. MED19 has been reported to be overexpressed in various cancers, promoting cancer progression; however, the underlying mechanisms remain elusive. Here, we unexpectedly discovered that the MED19 protein can localize to the nucleolus independently of the Mediator and directly bind ribosomal RNA. Further investigation revealed that MED19 promotes 2'-O-methylation modifications on rRNA. Fibrillarin (FBL) acts as the catalytic enzyme responsible for 2'-O-methylation. We found that MED19 can directly interact with FBL through liquid-liquid phase separation. This interaction potentially enhances catalytic efficiency by increasing the local molecular concentration. Mature ribosomes containing highly 2'-O-methylated rRNA can enhance the internal ribosome entry sites (IRES) initiated translation. c-Myc was a well-studied IRES-containing gene. We found that knockdown of MED19 significantly reduced the protein abundance of c-Myc without affecting its mRNA levels. Pan-cancer analyses also demonstrated a positive correlation between MED19 and c-Myc at the protein level but not the mRNA level. In summary, our study has identified a novel role for MED19 in translation regulation, distinct from its well-established function in transcriptional regulation.