Expression of the tumor-expressed protein MageB2 enhances rRNA transcription

AMATO, GASTÓN EZEQUIEL; PASCUCCI, FRANCO ANDRÉS; DARDIS, ANDREA; LADELFA, MARÍA FÁTIMA; ESCALADA, MICAELA CAROLINA; BENEVENTO, ANDRES FERNANDEZ; SCHNEIDER, CLAUDIO; PECHE, LETICIA YAMILA; ZAMPIERI, STEFANIA; DO PORTO, DARIO FERNANDEZ; MONTE, MARTIN

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

ELSEVIER SCIENCE BV

Año: 2021 vol. 1868

0167-4889

An essential requirement for cells to sustain a high proliferating rate is to be paired with enhanced protein synthesis through the production of ribosomes. For this reason, part of the growth-factor signaling pathways, are devoted to activate ribosome biogenesis. Enhanced production of ribosomes is a hallmark in cancer cells, which is boosted by different mechanisms. Here we report that the nucleolar tumor-protein MageB2, whose expression is associated with cell proliferation, also participates in ribosome biogenesis. Studies carried out in both siRNA-mediated MageB2 silenced cells and CRISPR/CAS9-mediated MageB2 knockout (KO) cells showed that its expression is linked to rRNA transcription increase independently of the cell proliferation status. Mechanistically, MageB2 interacts with phospho-UBF, a protein which causes the recruitment of RNA Pol I pre-initiation complex required for rRNA transcription. In addition, cells expressing MageB2 displays enhanced phospho-UBF occupancy at the rDNA gene promoter. Proteomic studies performed in MageB2 KO cells revealed impairment in ribosomal protein (RPs) content. Functionally, enhancement in rRNA production in MageB2 expressing cells, was directly associated with an increased dynamic in protein synthesis. Altogether our results unveil a novel function for a tumor-expressed protein from the MAGE-I family. Findings reported here suggest that nucleolar MageB2 might play a role in enhancing ribosome biogenesis as part of its repertoire to support cancer cell proliferation.