So Rolando B, Gonzales Bianca, Henning Dale, Dixon Jill, Dixon Michael J, Valdez Benigno C
Department of Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Gene. 2004 Mar 17;328:49-57. doi: 10.1016/j.gene.2003.11.027.
Treacher Collins syndrome (TCS) is characterized by an abnormality in craniofacial development during early embryogenesis. TCS is caused by mutations in the gene TCOF1, which encodes the nucleolar phosphoprotein treacle. Genetic and proteomic characterizations of TCS/treacle are based on the previously reported 26 exons of TCOF1. Here, we report the identification of 231-nucleotide (nt) exon 6A (between exons 6 and 7) and 108-nt exon 16A (between exons 16 and 17). Isoforms with exon 6A are up to 3.7-fold more abundant than alternatively spliced variants without exon 6A, but only minor isoforms contain exon 16A. Exon 6A encodes a peptide sequence containing basic and acidic domains similar to 10 other exons of TCOF1. Unlike the other exons, exon 6A encodes a nuclear localization signal (NLS) which does not, however, alter the nucleolar localization of full-length treacle. The discovery of exons 6A and 16A is relevant to mutational analysis of the TCOF1 gene in TCS patients, and to functional analysis of its gene product.
特雷彻·柯林斯综合征（TCS）的特征是在胚胎发育早期颅面发育异常。TCS由TCOF1基因突变引起，该基因编码核仁磷蛋白treacle。TCS/treacle的遗传和蛋白质组学特征基于先前报道的TCOF1的26个外显子。在此，我们报告了231个核苷酸（nt）的外显子6A（位于外显子6和7之间）和108 nt的外显子16A（位于外显子16和17之间）的鉴定。含有外显子6A的异构体比不含外显子6A的可变剪接变体丰富多达3.7倍，但只有少量异构体含有外显子16A。外显子6A编码一个肽序列，该序列包含与TCOF1的其他10个外显子相似的碱性和酸性结构域。与其他外显子不同，外显子6A编码一个核定位信号（NLS），然而，该信号不会改变全长treacle的核仁定位。外显子6A和16A的发现与TCS患者TCOF1基因的突变分析及其基因产物的功能分析相关。
