Alternative titles; symbols
HGNC Approved Gene Symbol: GRWD1
Cytogenetic location: 19q13.33 Genomic coordinates (GRCh38) : 19:48,445,983-48,457,022 (from NCBI)
GRWD1 is a component of the 50S and 80S preribosomal complexes and plays a role in ribosome biogenesis (Gratenstein et al., 2005).
By sequencing clones obtained from a size-fractionated fetal brain cDNA library, Nagase et al. (2001) cloned GRWD1, which they designated KIAA1942. The cDNA contains several repetitive elements in its 3-prime end, and the deduced 445-amino acid protein contains a WD domain. RT-PCR ELISA detected robust expression in all tissues and specific brain regions examined.
By screening a human myeloid leukemia cell line cDNA library with a GRWD1 fragment, followed by 5-prime RACE, Gratenstein et al. (2005) cloned full-length GRWD1. The deduced 446-amino acid protein contains a glutamic/aspartic acid-rich domain of 14 consecutive amino acids and 4 WD repeat domains. RNA dot blot analysis showed ubiquitous GRWD1 expression, with highest levels in liver, placenta, a transformed colorectal cell line, and a lung carcinoma cell line. Epitope-tagged GRWD1 was expressed mainly in the nucleus of transduced mouse fibroblasts, but some immunoreactivity was present in cytoplasm. Western blot analysis detected a major GRWD1 band at 62 kD and a minor band at 90 kD.
Using small interfering RNA (siRNA), Killian et al. (2004) showed that GRWD knockdown in a human colon carcinoma cell line had a dramatic effect on chromosome segregation and increased the number of abnormal mitoses. Fluorescence-tagged GRWD was detected in the nucleus or nucleolus during interphase, but it was also detected in the cytoplasm during mitosis.
Using Northern blot analysis, Gratenstein et al. (2005) found that in a human myeloid cell line induced to differentiate by vitamin D3 or retinoic acid, GRWD1 expression was downregulated coincident with slowing of cellular proliferation. Downregulation of GRWD1 with siRNA similarly resulted in decreased cellular proliferation in human embryonic kidney cells. Metabolic labeling of cells expressing GRWD1 siRNA showed decreased global protein synthesis. Nuclear fractionation studies showed that GRWD1 cosedimented with 50S and 80S preribosomal complexes and with BOP1 (610596), a protein implicated in ribosome biogenesis. RNase treatment shifted both GRWD1 and BOP1 to low molecular mass fractions. Gratenstein et al. (2005) concluded that GRWD1 plays a role in ribosome biogenesis and that during myeloid differentiation its levels are regulated.
Gratenstein et al. (2005) determined that the GRWD1 gene contains 7 exons and spans 7.9 kb. They identified 2 potential transcriptional regulatory regions, including an SP1 (189906) site and overlapping interferon regulatory binding sites.
By genomic sequence analysis, Gratenstein et al. (2005) mapped the GRWD1 gene to chromosome 19q13.3.
Gratenstein, K., Heggestad, A. D., Fortun, J., Notterpek, L., Pestov, D. G., Fletcher, B. S. The WD-repeat protein GRWD1: potential roles in myeloid differentiation and ribosome biogenesis. Genomics 85: 762-773, 2005. [PubMed: 15885502] [Full Text: https://doi.org/10.1016/j.ygeno.2005.02.010]
Killian, A., Le Meur, N., Sesboue, R., Bourguignon, J., Bougeard, G., Gautherot, J., Bastard, C., Frebourg, T., Flaman, J.-M. Inactivation of the RRB1-pescadillo pathway involved in ribosome biogenesis induces chromosomal instability. Oncogene 23: 8597-8602, 2004. [PubMed: 15467761] [Full Text: https://doi.org/10.1038/sj.onc.1207845]
Nagase, T., Kikuno, R., Ohara, O. Prediction of the coding sequences of unidentified human genes. XXII. The complete sequences of 50 new cDNA clones which code for large proteins. DNA Res. 8: 319-327, 2001. [PubMed: 11853319] [Full Text: https://doi.org/10.1093/dnares/8.6.319]