Anti-WBSCR22 monoclonal antibody Made to order

Williams-Beuren syndrome (WBS), due to a contiguous gene deletion of approximately 1.5 Mb at 7q11.23, is a complex developmental disorder with multisystemic manifestations including supravalvular aortic stenosis (SVAS) and a specific cognitive phenotype. Large repeats containing genes and pseudogenes flank the deletion break-points, and the mutation mechanism commonly appears to be unequal meiotic crossover. Except for elastin, hemizygosity of which is associated with supravalvular aortic stenosis, it is unknown which of the 18 genes in the deletion area contributes to the phenotype. Here, we report the identification and characterization of two novel genes, WBSCR20 and WBSCR22, which map to the common WBS deletion region. WBSCR22 encodes a putative methyltransferase protein strongly expressed in heart, skeletal muscle and kidney. WBSCR-20 encodes a novel protein expressed in skeletal muscle with similarity to p120 (NOL1), a 120-kDa proliferation-associated nucleolar antigen, a member of-an evolutionarily conserved protein Family. A highly similar putative gene, WBSCR20B, flanks the WBS deletion at the telomeric side. Hemizygous deletion of either of the novel genes might contribute to the growth retardation, the myopathy or the premature aging effects in the pathogenesis of WBS. Copyright (C) 2002 S. Karger AG, Basel.

Ribosomal (r) RNAs are extensively modified during ribosome synthesis and their modification is required for the fidelity and efficiency of translation. Besides numerous small nucleolar RNA-guided 2'-O methylations and pseudouridinylations, a number of individual RNA methyltransferases are involved in rRNA modification. WBSCR22/Merm1, which is affected in Williams-Beuren syndrome and has been implicated in tumorigenesis and metastasis formation, was recently shown to be involved in ribosome synthesis, but its molecular functions have remained elusive. Here we show that depletion of WBSCR22 leads to nuclear accumulation of 3'-extended 18SE pre-rRNA intermediates resulting in impaired 18S rRNA maturation. We map the 3' ends of the 18SE pre-rRNA intermediates accumulating after depletion of WBSCR22 and in control cells using 3'-RACE and deep sequencing. Furthermore, we demonstrate that WBSCR22 is required for N-7-methylation of G1639 in human 18S rRNA in vivo. Interestingly, the catalytic activity of WBSCR22 is not required for 18S pre-rRNA processing, suggesting that the key role of WBSCR22 in 40S subunit biogenesis is independent of its function as an RNA methyltransferase.