TCOF1

Template:Short description Template:Cs1 config An Error has occurred retrieving Wikidata item for infobox Treacle Ribosome Biogenesis Factor 1 (TCOF1) also known as Treacle is a protein that in humans is encoded by the TCOF1 gene. TCOF1 encodes a nucleolar protein with an LIS1 homology domain. 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.

Gene

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.

Function

TCOF1 is involved in the production of a molecule called ribosomal RNA (rRNA) within cells. TCOF1 is active in the nucleolus, which is a small region inside the nucleus where rRNA is produced. As a major component of cell structures called ribosomes, rRNA is essential for the assembly of proteins. This protein is active during early embryonic development in structures that become bones and other tissues in the face. 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.

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.

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.

Model organisms

Mutations in this gene in Jindo dogs have been associated to the observed cranial differences between Jindo and boxer dogs.

Further reading

• Splendore A, Silva EO, Alonso LG, Richieri-Costa A, Alonso N, Rosa A, et al. (October 2000). "High mutation detection rate in TCOF1 among Treacher Collins syndrome patients reveals clustering of mutations and 16 novel pathogenic changes". Human Mutation. 16 (4): 315–322. doi:10.1002/1098-1004(200010)16:4<315::AID-HUMU4>3.0.CO;2-H. PMID 11013442. S2CID 36109746.
• Dixon MJ, Dixon J, Raskova D, Le Beau MM, Williamson R, Klinger K, et al. (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. PMID 1303194.
• 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. PMID 8125298.
• Dixon MJ, Dixon J, Houseal T, Bhatt M, Ward DC, Klinger K, et al. (May 1993). "Narrowing the position of the Treacher Collins syndrome locus to a small interval between three new microsatellite markers at 5q32-33.1". American Journal of Human Genetics. 52 (5): 907–914. PMC 1682053. PMID 8488840.
• "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. PMID 8563749. S2CID 34312227.
• Bonaldo MF, Lennon G, Soares MB (September 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
• Edwards SJ, Gladwin AJ, Dixon MJ (March 1997). "The mutational spectrum in Treacher Collins syndrome reveals a predominance of mutations that create a premature-termination codon". American Journal of Human Genetics. 60 (3): 515–524. PMC 1712503. PMID 9042910.
• Dixon J, Edwards SJ, Anderson I, Brass A, Scambler PJ, Dixon MJ (March 1997). "Identification of the complete coding sequence and genomic organization of the Treacher Collins syndrome gene". Genome Research. 7 (3): 223–234. doi:10.1101/gr.7.3.223. PMID 9074926.
• Wise CA, Chiang LC, Paznekas WA, Sharma M, Musy MM, Ashley JA, et al. (April 1997). "TCOF1 gene encodes a putative nucleolar phosphoprotein that exhibits mutations in Treacher Collins Syndrome throughout its coding region". Proceedings of the National Academy of Sciences of the United States of America. 94 (7): 3110–3115. Bibcode:1997PNAS...94.3110W. doi:10.1073/pnas.94.7.3110. PMC 20330. PMID 9096354.
• Paznekas WA, Zhang N, Gridley T, Jabs EW (September 1997). "Mouse TCOF1 is expressed widely, has motifs conserved in nucleolar phosphoproteins, and maps to chromosome 18". Biochemical and Biophysical Research Communications. 238 (1): 1–6. doi:10.1006/bbrc.1997.7229. PMID 9299440.
• 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. PMID 9373149.
• Marsh KL, Dixon J, Dixon MJ (October 1998). "Mutations in the Treacher Collins syndrome gene lead to mislocalization of the nucleolar protein treacle". Human Molecular Genetics. 7 (11): 1795–1800. doi:10.1093/hmg/7.11.1795. PMID 9736782.
• Winokur ST, Shiang R (November 1998). "The Treacher Collins syndrome (TCOF1) gene product, treacle, is targeted to the nucleolus by signals in its C-terminus". Human Molecular Genetics. 7 (12): 1947–1952. doi:10.1093/hmg/7.12.1947. PMID 9811939.
• Jones NC, Farlie PG, Minichiello J, Newgreen DF (November 1999). "Detection of an appropriate kinase activity in branchial arches I and II that coincides with peak expression of the Treacher Collins syndrome gene product, treacle". Human Molecular Genetics. 8 (12): 2239–2245. doi:10.1093/hmg/8.12.2239. PMID 10545604.
• Isaac C, Marsh KL, Paznekas WA, Dixon J, Dixon MJ, Jabs EW, et al. (September 2000). "Characterization of the nucleolar gene product, treacle, in Treacher Collins syndrome". Molecular Biology of the Cell. 11 (9): 3061–3071. doi:10.1091/mbc.11.9.3061. PMC 14975. PMID 10982400.
• Emes RD, Ponting CP (November 2001). "A new sequence motif linking lissencephaly, Treacher Collins and oral-facial-digital type 1 syndromes, microtubule dynamics and cell migration". Human Molecular Genetics. 10 (24): 2813–2820. doi:10.1093/hmg/10.24.2813. PMID 11734546.
• Splendore A, Jabs EW, Passos-Bueno MR (July 2002). "Screening of TCOF1 in patients from different populations: confirmation of mutational hot spots and identification of a novel missense mutation that suggests an important functional domain in the protein treacle". Journal of Medical Genetics. 39 (7): 493–495. doi:10.1136/jmg.39.7.493. PMC 1735178. PMID 12114482.
• Ohta S, Shiomi Y, Sugimoto K, Obuse C, Tsurimoto T (October 2002). "A proteomics approach to identify proliferating cell nuclear antigen (PCNA)-binding proteins in human cell lysates. Identification of the human CHL12/RFCs2-5 complex as a novel PCNA-binding protein". The Journal of Biological Chemistry. 277 (43): 40362–40367. doi:10.1074/jbc.M206194200. PMID 12171929.

External links

• GeneReviews/NCBI/NIH/UW entry on Treacher Collins Syndrome or Mandibulofacial Dysostosis
• GeneCard
• TCOF1+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• TCOF1 human gene location in the UCSC Genome Browser.
• TCOF1 human gene details in the UCSC Genome Browser.