Reduced Translation Efficiency Due to Novel Splicing Variants in 5' Untranslated Region and Identification of Novel Cis-regulatory Elements in Canine and Human BRCA2

Overview

Journal BMC Mol Cell Biol

Publisher Biomed Central

Specialty Cell Biology

Date 2021 Jan 7

PMID 33407082

Citations 1

Authors

Yasunaga Yoshikawa

Hajime Kozuma

Masami Morimatsu

Kaori Sugawara

Koichi Orino

Affiliations

Soon will be listed here.

Abstract

Background: 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.

Results: 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.

Conclusions: 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.

Citing Articles

Detection of Germline Variants in 450 Breast/Ovarian Cancer Families with a Multi-Gene Panel Including Coding and Regulatory Regions.

Guglielmi C, Scarpitta R, Gambino G, Conti E, Belle F, Tancredi M Int J Mol Sci. 2021; 22(14).

PMID: 34299313 PMC: 8305371. DOI: 10.3390/ijms22147693.

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