%0 Journal Article
%T Genomic characterization of the human mitochondrial tumor suppressor gene 1 (MTUS1): 5' cloning and preliminary analysis of the multiple gene promoters
%A Jinsheng Yu
%A Xiqiang Liu
%A Hui Ye
%A Xiaofeng Zhou
%J BMC Research Notes
%D 2009
%I BioMed Central
%R 10.1186/1756-0500-2-109
%X Here, we characterized the 5' untranslated regions of the different transcript variants. We also cloned and functionally tested the alternatively utilized gene promoters that contribute to the production of different MTUS1 transcript variants.Our results confirmed the early hypothesis that the transcript variants of MTUS1 gene are driven by multiple gene promoters.The MTUS1 gene is located in a region (8p22) that shows frequent loss of heterozygosity (LOH) in several tumor types, including oral cancer [1]. Alternative exon utilization leads to the production of 5 known transcript variants (designated as variant 1 to 5) [2]. It has been suggested that the long form of transcript variants (variant 1, 2, and 3) are driven by a common gene promoter, while variant 4 and 5 are driven by 2 additional promoters [2]. Variant 5 was the first transcript variant to be cloned independently in 2 laboratories, as a gene that is transiently upregulated during initiation of cell differentiation and quiescence [3]. It represents an early component of the growth-inhibiting signaling cascade that interacts with angiotensin II AT2 receptor [4]. Evidence supporting the tumor suppressor function of other MTUS1 variants comes from the study on Xenopus Icis gene, a homolog of MTUS1 variants 1 and 2, which regulates microtubule growth and spindle formation prior to anaphase [5]. Here, we refined the genomic structure of the MTUS1 gene and functionally cloned the alternatively utilized gene promoters that control the production of these MTUS1 transcript variants. This will enhance our understanding on the regulation of this candidate tumor suppressor gene.To characterize the 5' untranslated regions (5'-UTR) of the MTUS1 transcript variants, 5'-RACE assays were carried out using human brain reference mRNA (Ambion Inc) and a FirstChoice RLM-RACE kit from Ambion, with primers specific for various transcript variants (Additional file 1). The RACE products were PCR amplified, gel purified and then
%U http://www.biomedcentral.com/1756-0500/2/109