Treacle Ribosome Biogenesis Factor 1 (TCOF1) also known as Treacle is a protein that in humans is encoded by the TCOF1gene.[5][6] TCOF1 encodes a nucleolar protein with an LIS1 homology domain.[7] The treacle protein is involved in rRNA gene transcription through its interaction with upstream binding factor (UBF). Mutations in this gene have been associated with Treacher Collins syndrome, a disorder which includes abnormal craniofacial development. Alternate transcriptional splice variants encoding different isoforms have been found for this gene, but only three of them have been characterized to date.[6]
The TCOF1 gene is located on the long (q) arm of chromosome 5 between positions 32 and 33.1, from base pair 150,357,629 to base pair 150,400,308.[8]
Function
TCOF1 is involved in the production of a molecule called ribosomal RNA (rRNA) within cells.[7] TCOF1 is active in the nucleolus, which is a small region inside the nucleus where rRNA is produced.[9] As a major component of cell structures called ribosomes, rRNA is essential for the assembly of proteins.[10] This protein is active during early embryonic development in structures that become bones and other tissues in the face.[11] Although the precise function of this protein is unknown, researchers believe that it plays a critical role in the development of facial bones and related structures.[12]
Aside from its interaction with UBF, treacle has been implicated in the methylation of the precursor to mature ribosomal RNA by interaction with the nucleolar protein pNop56.[13]
Clinical significance
More than 120 mutations in the TCOF1 gene have been identified in people with Treacher Collins syndrome. Most of these mutations insert or delete a small number of DNA building blocks (base pairs) in the TCOF1 gene. TCOF1 mutations lead to the production of an abnormally small, nonfunctional version of treacle or prevent the cell from producing this protein. Researchers speculate that a loss of treacle reduces the production of rRNA in parts of the embryo that develop into facial bones and tissues. It is not known how loss of the treacle protein causes the specific problems with facial development found in Treacher Collins syndrome. For instance, mutations in the TCOF gene of these individuals often result in a cleft palate.[14]
Model organisms
Mutations in this gene in Jindo dogs have been associated to the observed cranial differences between Jindo and boxer dogs.[15]
↑ Dixon J, Jones NC, Sandell LL, Jayasinghe SM, Crane J, Rey JP, etal. (September 2006). "Tcof1/Treacle is required for neural crest cell formation and proliferation deficiencies that cause craniofacial abnormalities". Proceedings of the National Academy of Sciences of the United States of America. 103 (36): 13403–13408. doi:10.1073/pnas.0603730103. PMID16938878.
Dixon MJ, Dixon J, Raskova D, Le Beau MM, Williamson R, Klinger K, etal. (July 1992). "Genetic and physical mapping of the Treacher Collins syndrome locus: refinement of the localization to chromosome 5q32-33.2". Human Molecular Genetics. 1 (4): 249–253. doi:10.1093/hmg/1.4.249. PMID1303194.
Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–174. doi:10.1016/0378-1119(94)90802-8. PMID8125298.
"Positional cloning of a gene involved in the pathogenesis of Treacher Collins syndrome. The Treacher Collins Syndrome Collaborative Group". Nature Genetics. 12 (2): 130–136. February 1996. doi:10.1038/ng0296-130. PMID8563749. S2CID34312227.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–156. doi:10.1016/S0378-1119(97)00411-3. PMID9373149.
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