Breast cancer 2, early onset (BRCA2) is a tumor suppressor gene. The protein encoded by this gene plays an important role in homologous recombination (HR)-mediated DNA repair. Deleterious mutations in BRCA2 and downregulation of its expression have been associated with tumorigenesis in dogs and humans. Thus, regulation of BRCA2 expression level is important for maintaining homeostasis in homologous recombination. In this study, the mechanisms that regulate the expression of BRCA2 were proposed. Novel splicing variants were identified in the 5′ untranslated region (UTR) of canine and human BRCA2 in canine testis, canine ovary, and canine and human cultured cell lines. In cultured cells, the ratio of BRCA2 splicing variants at the 5′ UTR was altered by serum starvation. These novel splicing variants, excluding one of the canine splicing variants, were found to reduce the translational efficiency. Additionally, the DNA sequence in human BRCA2 intron 1 harbored novel cis-regulatory elements. Three silencer and two enhancer cis-regulatory elements were identified in human BRCA2 intron 1. This study demonstrates that BRCA2 expression level is regulated via 5′ UTR splicing variants and that the BRCA2 intron 1 region harbors cis-regulatory elements.

中文翻译：

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由于 5' 非翻译区中的新剪接变体以及犬和人 BRCA2 中新的顺式调控元件的鉴定导致翻译效率降低

2、早发性乳腺癌（BRCA2）是一种抑癌基因。该基因编码的蛋白质在同源重组 (HR) 介导的 DNA 修复中起重要作用。BRCA2 的有害突变及其表达的下调与狗和人类的肿瘤发生有关。因此，调节 BRCA2 表达水平对于维持同源重组中的稳态很重要。在这项研究中，提出了调节 BRCA2 表达的机制。在犬睾丸、犬卵巢以及犬和人类培养细胞系中犬和人 BRCA2 的 5' 非翻译区 (UTR) 中发现了新的剪接变体。在培养的细胞中，血清饥饿改变了 5' UTR 处 BRCA2 剪接变体的比例。这些新的剪接变体，不包括犬类剪接变体之一，发现会降低翻译效率。此外，人类 BRCA2 内含子 1 中的 DNA 序列含有新的顺式调控元件。在人 BRCA2 内含子 1 中鉴定出三个沉默子和两个增强子顺式调节元件。该研究表明 BRCA2 表达水平是通过 5' UTR 剪接变体调节的，并且 BRCA2 内含子 1 区域含有顺式调节元件。