Hyperactive ribosomal biogenesis is widely observed in
cancer, which has been partly attributed to the increased
rDNA transcription by Pol I in
cancer. However, whether small nucleolar RNAs (snoRNAs), a class of non-coding RNAs crucial in
ribosomal RNA (rRNA) maturation and functionality, are involved in
cancer remains elusive. We report that snoRNAs and
fibrillarin (FBL, an enzymatic
small nucleolar ribonucleoprotein,
snoRNP) are frequently overexpressed in both murine and human
breast cancer as well as in
prostate cancers, and significantly, that this overexpression is essential for tumorigenicity in vitro and in vivo. We demonstrate that when the elevated
snoRNA pathway is suppressed, the
tumor suppressor p53 can act as a sentinel of
snoRNP perturbation, the activation of which mediates the growth inhibitory effect. On the other hand, high level of FBL interferes with the activation of p53 by stress. We further show that p53 activation by FBL knockdown is not only regulated by the ribosomal protein-MDM2-mediated
protein stabilization pathway, but also by enhanced PTB-dependent, cap-independent translation. Together, our data uncover an essential role of deregulated
snoRNA biogenesis in
tumors and a new mechanism of nucleolar modulation of p53.