Abstract
BackgroundThe genetic basis of telomere length heterogeneity among mammalian species is still not well understood. Recently, a gene named regulator of telomere length elongation helicase (RTEL) was identified and predicted to be an essential participant in species-specific telomere length regulation in two murine species. To obtain broader insights into its structure and biological functions and to ascertain whether RTEL is also a candidate gene in the regulation of telomere length diversity in other mammalian species, data from other mammals may be helpful.ResultsHere we report the cDNA cloning, genomic structure, chromosomal location, alternative splicing pattern, expression distribution and DNA methylation profile of the bovine homolog of RTEL. The longest transcript of bovine RTEL is 4440 nt, encompassing 24.8 kb of genomic sequence that was mapped to chromosome 13q2.2. It encodes a conserved helicase-like protein containing seven characterized helicase motifs in the first 750 aa and a PIP box in the C-terminus. Four splice variants were identified within the transcripts in both the coding and 5'-untranslated regions; Western blot revealed that the most abundant splice variant SV-1 was translated to a truncated isoform of RTEL. The different 5'UTRs imply alternative transcription start sites in the promoter; Bovine RTEL was transcribed at the blastocyst stage, and expression levels were highest in adult testis, liver and ovary. DNA methylation analysis of tissues that differed significantly in expression level indicated that relatively low DNA methylation is associated with higher expression.ConclusionIn this study, we have identified and characterized a bovine RTEL homolog and obtained basic information about it, including gene structure, expression distribution, splice variants and profile of DNA methylation around two putative transcription start sites. These data may be helpful for further comparative and functional analysis of RTEL in mammals.
Highlights
The genetic basis of telomere length heterogeneity among mammalian species is still not well understood
Using two sets of primers, the coding region of bovine regulator of telomere length elongation helicase (RTEL) was amplified in two overlapping fragments (1.9 kb and 2.1 kb respectively) by RT-PCR
SV-1, where the PIP box is absent from the protein sequence, would be helpful for investigating the function of PIP and the functional relationship of RTEL and proliferating cell nuclear antigen (PCNA), and we have demonstrated that SV-1 translated to a truncated protein by Western blot
Summary
The genetic basis of telomere length heterogeneity among mammalian species is still not well understood. A gene named regulator of telomere length elongation helicase (RTEL) was identified and predicted to be an essential participant in species-specific telomere length regulation in two murine species. A novel gene named regulator of telomere length elongation helicase (RTEL), which encodes a helicase-like protein with several functional helicase domains/motifs, was shown to participate in telomere length regulation in two murine species [9,32]. By incorporating phenotypic data from RTEL knock-out ES cells and comparing the function of a nematode homolog gene named dog-1 (deletion of G tracts) [11], RTEL is predicted to unwind "harmful" structures that form in the G-rich region of genome, especially the telomeric DNA, in order to protect the telomere and influence the length balance [9]. As a safeguard for the genome, it contributes to the maintenance of genetic stability by minimizing unexpected recombinations induced by Gquadruplex
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