Ribin, a Protein Encoded by a Message Complementary to rRNA, Modulates Ribosomal Transcription and Cell Proliferation

Abstract

The control of rRNA transcription, tightly coupled to the cell cycle and growth state of the cell, is a key process for understanding the mechanisms that drive cell proliferation. Here we describe a novel protein, ribin, found in rodents, that binds to the rRNA promoter and stimulates its activity. The protein also interacts with the basal rRNA transcription factor UBF. The open reading frame encoding ribin is 96% complementary to a central region of the large rRNA. This demonstrates that ribosomal DNA-related sequences in higher eukaryotes can be expressed as protein-coding messages. Ribin contains two predicted nuclear localization sequence elements, and green fluorescent protein-ribin fusion proteins localize in the nucleus. Cell lines overexpressing ribin exhibit enhanced rRNA transcription and faster growth. Furthermore, these cells significantly overcome the suppression of rRNA synthesis caused by serum deprivation. On the other hand, the endogenous ribin level correlates positively with the amount of serum in the medium. The data show that ribin is a limiting stimulatory factor for rRNA synthesis in vivo and suggest its involvement in the pathway that adapts ribosomal transcription and cell proliferation to physiological changes.