RGD Reference Report - Fundamental cellular processes do not require vertebrate-specific sequences within the TATA-binding protein. - Rat Genome Database

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Fundamental cellular processes do not require vertebrate-specific sequences within the TATA-binding protein.

Authors: Schmidt, EE  Bondareva, AA  Radke, JR  Capecchi, MR 
Citation: Schmidt EE, etal., J Biol Chem 2003 Feb 21;278(8):6168-74. Epub 2002 Dec 5.
RGD ID: 1299882
Pubmed: PMID:12471023   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M211205200   (Journal Full-text)

The 180-amino acid core of the TATA-binding protein (TBPcore) is conserved from Archae bacteria to man. Vertebrate TBPs contain, in addition, a large and highly conserved N-terminal region that is not found in other phyla. We have generated a line of mice in which the tbp allele is replaced with a version, tbp(Delta N), which lacks 111 of 135 N-terminal amino acid residues. Most tbp(Delta N/Delta N) fetuses die in midgestation. To test whether a disruption of general cellular processes contributed to this fetal loss, primary fibroblast cultures were established from +/+, Delta N/+, and Delta N/Delta N fetuses. The cultures exhibited no genotype-dependent differences in proliferation or in expression of the proliferative markers dihydrofolate reductase (DHFR) mRNA (S phase-specific) and cdc25B mRNA (G(2)-specific). The mutation had no effect on transcription initiation site fidelity by either RNA polymerase II (pol II) or pol III. Moreover, the mutation did not cause differences in levels of U6 RNA, a pol III-dependent component of the splicing machinery, in mRNA splicing efficiency, in expression of housekeeping genes from either TATA-containing or TATA-less promoters, or in global gene expression. Our results indicated that general eukaryotic cell functions are unaffected by deletion of these vertebrate-specific sequences from TBP. Thus, all activities of this polypeptide domain must either be compensated for by redundant activities or be restricted to situations that are not represented by primary fibroblasts.

Objects referenced in this article
Gene Cdc25b cell division cycle 25B Mus musculus
Gene Cdc25c cell division cycle 25C Mus musculus
Gene Tbp TATA box binding protein Mus musculus
Gene Tbpl1 TATA box binding protein-like 1 Mus musculus
Gene Tbp TATA box binding protein Rattus norvegicus

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