Identification of the small protein rich in arginine and glycine (SRAG): a newly identified nucleolar protein that can regulate cell proliferation.

The characterization of new proteins will aid in our explanation of normal biology and disease. Toward that goal, we describe the initial characterization of the small protein rich in arginine and glycine (SRAG). Human and mouse SRAG are 248/249-amino acid arginine- and glycine-rich proteins that are widely expressed in tissues and cell lines. Two SRAG isoforms, SRAG-5 and SRAG-3, which are truncations of full-length SRAG, were also identified. Although all SRAG proteins reside in the nucleus, they were also found within the nucleolus. Localization within the nucleolus was regulated by the N terminus of the protein. Our initial studies indicated that SRAG can interact with RNA. Full-length SRAG protein levels were highest in resting cells and were reduced in proliferating cells. The reduction in SRAG protein that occurs in proliferating cells was mapped with inhibitors to the G(2)/M phase of the cell cycle. As expected, the overexpression of SRAG reduced the percentage of cells in the G(2)/M phase and increased cell death. In sum, we have identified a new and intriguing member of the nucleolar proteome.