The Human WBSCR22 Protein Is Involved in the Biogenesis of the 40S Ribosomal Subunits in Mammalian Cells

Abstract

The human WBSCR22 protein was previously shown to be up-regulated in invasive breast cancer and its ectopic expression enhances tumor cell survival in the vasculature. In the current study, we show that the WBSCR22 protein is important for cell growth. Knock-down of WBSCR22 with siRNA results in slower growth of WBSCR22-depleted cells. Treatment with siWBSCR22 causes defects in the processing of pre-rRNAs and reduces the level of free 40S ribosomal subunit, suggesting that WBSCR22 is involved in ribosome small subunit biosynthesis. The human WBSCR22 partially complements the growth of WBSCR22 yeast homologue, bud23 deletion mutant suggesting that the human WBSCR22 is a functional homologue of yeast Bud23. WBSCR22 is localized throughout the cell nucleus and is not stably associated with ribosomal subunits within the cell nucleus. We also show that the WBSCR22 protein level is decreased in lymphoblastoid cell lines derived from William-Beuren Syndrome (WBS) patients compared to healthy controls. Our data suggest that the WBSCR22 protein is a ribosome biogenesis factor involved in the biosynthesis of 40S ribosomal particles in mammalian cells.

Retracted: Ribosomal Protein S15A Augments Human Osteosarcoma Cell Proliferation In Vitro

“…WBSCR22 knockdown leads to defects in the processing of pre-rRNAs and decreases the level of the free 40S ribosomal subunit. 24 Ribosomal protein S6 (RPS6), a key regulator of 40S ribosome biogenesis, has been shown to participate in human esophageal cancer progression. RPS6 knockdown resulted in a reduction in esophageal cancer cell growth, migration, and invasion, and cyclin D1 is involved in the process.…”

WBSCR22/Merm1 is required for late nuclear pre-ribosomal RNA processing and mediates N7-methylation of G1639 in human 18S rRNA

“…Depletion of WBSCR22 leads to accumulation of 3 ′ -extended 18SE pre-rRNAs in the nucleus WBSCR22/Merm1 was recently shown to be involved in the biogenesis of the 40S ribosomal subunit (Õunap et al 2013;Tafforeau et al 2013). To get further insight into the molecular function of WBSCR22 in ribosome biogenesis we investigated the pre-rRNA processing defect in more detail.…”

“…A loss of WBSCR22 was detected in inflammatory and neoplastic lung pathologies and the protein has been linked to glucocorticoid receptor regulation of histone modification (Jangani et al 2014). Recently, WBSCR22 was shown to be required for the biogenesis of the small ribosomal subunit (Wild et al 2010;Õunap et al 2013;Tafforeau et al 2013), but its molecular function has remained unclear.…”

Ribosomal protein S15A promotes malignant transformation and predicts poor outcome in colorectal cancer through misregulation of p53 signaling pathway

“…To date, a number of oncogenic or tumor suppressive genes have been identified to affect the formation of mature ribosome (12)(13)(14)(15), which suggest that protein synthesis machinery plays an important role in the regulation of malignant transformation. For instance, the oncogenic wBSCR22 protein, important for ribosome small subunit biosynthesis, is (16). Ribosomal protein S6 (RPS6), a key regulator of 40S ribosome biogenesis, actively participates in human esophageal cancer progression.…”