Critical role for nucleostemin in protein synthesis and muscle cell differentiation

Abstract

Nucleostemin (NS) is a nucleolar protein that was shown to be primarily expressed in proliferating cells and essential for proliferation but the precise functions of NS remained unclear. Here, we reveal a significant role for NS as an integrated component of ribosome biogenesis, particularly pre‐rRNA processing. The supporting data demonstrated physical interactions of NS with other processing‐related proteins, nucleolar retention of these proteins by NS, and inhibition of pre‐rRNA processing and protein synthesis in NS‐depleted cells. We also showed that unlike in other cell lineages, NS was not downregulated in differentiated skeletal muscle cells, which maintain highly active protein synthesis after exit from the cell cycle. Moreover, progress of muscle differentiation could be modulated by NS in a dose‐dependent manner. These results underscore a fundamental involvement of NS in cell proliferation and differentiation through its contribution to ribosome biogenesis and protein synthesis.This work was supported by Muscular Dystrophy Association, Korea Institute of Science and Technology, Nash Foundation and the NIH.