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编码一种类似于FUS/TLS和EWS蛋白的假定RNA结合蛋白的人类RBP56基因的克隆与定位。

Cloning and mapping of a human RBP56 gene encoding a putative RNA binding protein similar to FUS/TLS and EWS proteins.

作者信息

Morohoshi F, Arai K, Takahashi E I, Tanigami A, Ohki M

机构信息

Radiobiology Division, National Cancer Center Research Institute, Tokyo, Japan.

出版信息

Genomics. 1996 Nov 15;38(1):51-7. doi: 10.1006/geno.1996.0591.

Abstract

The EWS gene was found at the chromosome breakpoints in Ewing sarcoma, and the FUS/TLS gene was found at the breakpoints of myxoid liposarcoma and acute myeloid leukemia. These genes encode proteins that carry a highly homologous RNA binding domain. Fusion proteins made of the N-terminal half of EWS or FUS/TLS and transcriptional regulatory proteins, also derived from genes located at breakpoints, have been suggested to be involved in the pathogenesis of tumors. By PCR amplification of human Namalwa cell cDNA using degenerate primers made from the conserved amino acid sequences in the RNA binding domain of EWS and FUS/TLS, we obtained a cDNA fragment (RBP56 cDNA), the predicted amino acid sequences of which were similar but not identical to those of EWS and FUS/TLS. Using this fragment as a probe, we obtained two isoforms of cDNAs consisting of 2144 and 2153 bp, respectively, which encode proteins consisting of 589 and 592 amino acid residues, respectively. The predicted amino acid sequences of RBP56 protein have a serine-, tyrosine-, glutamine-, and glycine-rich region in the N-terminal region, an RNA binding domain and a C2C2 finger motif in the central region, and degenerate repeats of DR(S)GG(G)-YGG sequences in the C-terminal region. The expression of RBP56 mRNA was observed in all of the human fetal and adult tissues examined, as was the expression of EWS and FUS/TLS mRNAs. The RBP56 gene was mapped to chromosome 17q11.2 to q12.

摘要

在尤因肉瘤的染色体断点处发现了EWS基因,在黏液样脂肪肉瘤和急性髓系白血病的断点处发现了FUS/TLS基因。这些基因编码的蛋白质带有高度同源的RNA结合结构域。由EWS或FUS/TLS的N端一半与同样源自断点处基因的转录调节蛋白组成的融合蛋白,被认为与肿瘤的发病机制有关。通过使用由EWS和FUS/TLS的RNA结合结构域中保守氨基酸序列制成的简并引物对人Namalwa细胞cDNA进行PCR扩增,我们获得了一个cDNA片段(RBP56 cDNA),其预测的氨基酸序列与EWS和FUS/TLS的相似但不相同。用该片段作为探针,我们获得了分别由2144和2153 bp组成的两种cDNA异构体,它们分别编码由589和592个氨基酸残基组成的蛋白质。RBP56蛋白的预测氨基酸序列在N端区域有一个富含丝氨酸、酪氨酸、谷氨酰胺和甘氨酸的区域,在中央区域有一个RNA结合结构域和一个C2C2指状基序,在C端区域有DR(S)GG(G)-YGG序列的简并重复。在所检测的所有人类胎儿和成人组织中均观察到RBP56 mRNA的表达,EWS和FUS/TLS mRNA的表达情况也是如此。RBP56基因定位于染色体17q11.2至q12。

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