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DEAH-BOX HELICASE 33; DHX33

DEAH-BOX HELICASE 33; DHX33

Alternative titles; symbolsDEAH-BOX POLYPEPTIDE 33HGNC Approved Gene Symbol: DHX33Cytogenetic location: 17p13.2 Genomic coordinates (GRCh38): 17:5,440,916-5,...

Alternative titles; symbols

  • DEAH-BOX POLYPEPTIDE 33

HGNC Approved Gene Symbol: DHX33

Cytogenetic location: 17p13.2 Genomic coordinates (GRCh38): 17:5,440,916-5,469,054 (from NCBI)

▼ Description
Members of the DEAD/DEAH box family of RNA helicases, such as DHX33, modify the higher-order structure of RNA through hydrolysis of ATP or other nucleoside triphosphates (NTPs). These enzymes have a role in RNA transcription, RNA editing, pre-mRNA splicing, ribosome biogenesis, and RNA decay (summary by Zhang et al., 2011).

▼ Cloning and Expression
Ribosomal RNA (rRNA) is transcribed by RNA polymerase I (see POLR1B; 602000) as a 47S polycistronic precursor that is processed into mature 18S, 5.8S, and 28S rRNAs. Using an RNA interference screen to identify DDX/DHX enzymes that perturb rRNA transcription in human fibroblasts, Zhang et al. (2011) identified DHX33. The deduced protein contains an N-terminal ATP/NTP-binding domain, a central ATP/NTPase domain, and C-terminal helicase and ATP/NTP hydrolysis-dependent substrate interaction motifs. Fractionation of a human breast cancer cell line and human and mouse fibroblasts, as well as immunohistochemical analysis, revealed that DHX33 localized predominantly with markers of nucleoli, with some localization in nucleoplasm. Following dispersal of nucleoli during the cell cycle, DHX33 followed nucleolar proteins to nucleolar organizing regions.

▼ Gene Function
Zhang et al. (2011) found that knockdown of DHX33 in human cell lines inhibited rRNA transcription and processing, reduced the size of nucleoli, caused nucleolar stress, and initiated a p53 (TP53; 191170)-dependent stress response that included cell cycle arrest and induction of p21 (CDKN1A; 116899). Mutation analysis revealed that lys94 (K94) within the catalytic domain of DHX33 was crucial for rRNA transcription. DHX33 deficiency reduced recruitment of the large RNA polymerase subunit RPA194 (POLR1A; 616404) to rDNA loci and reduced phosphorylation of UBF (UBTF; 600673), which is required for RNA polymerase I activity. Overexpression of wildtype DHX33, but not DHX33 with a K94 mutation, in human cell lines stimulated 47S synthesis. Overexpression of DHX33 with deletion of its putative DNA-binding domain also reduced rRNA synthesis. Chromatin immunoprecipitation analysis of human breast cancer cells revealed that DHX33, like RPA194, occupied the entire rDNA promoter and transcribed regions, and binding required the DNA-binding motif of DHX33. DHX33 also immunoprecipitated with UBF. Zhang et al. (2011) concluded that DHX33 has a critical role in cell growth and rRNA synthesis.

▼ Mapping
Hartz (2011) mapped the DHX33 gene to chromosome 17p13.2 based on an alignment of the DHX33 sequence (GenBank AL359945) with the genomic sequence (GRCh37).

Tags: 17p13.2