Cloning of a human gene closely related to the genes coding for the c-myc single-strand binding proteins

Southwestern screening of human fibroblast cDNAs with an upstream element o f the alpha 2(I) collagen promoter (Box 5A) has led to the identification o f a novel gene product (RBMS3). RBMS3 contains two pairs of RNA binding mot ifs and is very closely related to the structure of the c-myc gene single-s trand binding proteins (MSSPs). MSSPs are believed to regulate DNA replicat ion, transcription, apopotosis and cell cycle progression by interacting wi th the C-MYC protein. Consonant with this postulate, RBMS3 binds in vitro t o the minus strand of Box 5A and transactivates transcription in the chimer ic GAL4 hybrid system. However, the RBMS3 protein mostly localizes to the c ytoplasm of transfected cells, in addition to binding strongly in vitro to synthetic poly-U and poly-A oligoribonucleotides. Finally, overexpression i n transfected fibroblasts of RBMS3 with and without a nuclear localization signal has no effect on Box SA-driven transcription. The results thus exclu de RBMS3 involvement in the transcriptional regulation of COL1A2 and strong ly suggest a cytoplasmic function of this new member of the MSSP family. As part of the initial characterization of RBMS3 we have also established tha t the gene resides on human chromosome 3p23-p24 and is widely expressed in the embryo and in the adult organism. (C) 2000 Elsevier Science B.V. All ri ghts reserved.