Radiation exposure can evoke cellular stress responses. Emerging recognition that long non-coding RNAs (lncRNAs) act as regulators of gene expression has broadened the spectra of molecules controlling the genomic landscape upon alterations in environmental conditions. Knowledge of the mechanisms responding to low dose irradiation (LDR) exposure is very limited yet most likely involve subtle ancillary molecular pathways other than those protecting the cell from direct cellular damage. The discovery that transcription of the lncRNA PARTICLE (promoter of MAT2A- antisense radiation-induced circulating lncRNA; PARTICL) becomes dramatically instigated within a day after LDR exposure introduced a new gene regulator onto the biological landscape. PARTICLE affords an RNA binding platform for genomic silencers such as DNA methyltransferase 1 and histone tri-methyltransferases to reign in the expression of tumor suppressors such as its neighboring MAT2A in cis as well as WWOX in trans. In silico evidence offers scope to speculate that PARTICLE exploits the abundance of Hoogsten bonds that exist throughout mammalian genomes for triplex formation, presumably a vital feature within this RNA silencer. PARTICLE may provide a buffering riboswitch platform for S-adenosylmethionine. The correlation of PARTICLE triplex formation sites within tumor suppressor genes and their abundance throughout the genome at cancer-related hotspots offers an insight into potential avenues worth exploring in future therapeutic endeavors.
- MeSH
- dávka záření MeSH
- DNA-(cytosin-5)-methyltransferasa 1 genetika MeSH
- genom lidský účinky záření MeSH
- genomika MeSH
- histonové methyltransferasy genetika MeSH
- lidé MeSH
- methioninadenosyltransferasa genetika MeSH
- nádorové supresorové proteiny genetika MeSH
- nádory genetika radioterapie MeSH
- oxidoreduktasa obsahující WW doménu genetika MeSH
- promotorové oblasti (genetika) genetika MeSH
- radiační expozice škodlivé účinky MeSH
- regulace genové exprese u nádorů účinky záření MeSH
- RNA dlouhá nekódující genetika MeSH
- RNA interference účinky záření MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Methionine adenosyltransferase (MAT) is a ubiquitous essential enzyme that, in eukaryotes, occurs in two relatively divergent paralogues: MAT and MATX. MATX has a punctate distribution across the tree of eukaryotes and, except for a few cases, is mutually exclusive with MAT. This phylogenetic pattern could have arisen by either differential loss of old paralogues or the spread of one of these paralogues by horizontal gene transfer. Our aim was to map the distribution of MAT/MATX genes within the Euglenida in order to more comprehensively characterize the evolutionary history of MATX. RESULTS: We generated 26 new sequences from 23 different lineages of euglenids and one prasinophyte alga Pyramimonas parkeae. MATX was present only in photoautotrophic euglenids. The mixotroph Rapaza viridis and the prasinophyte alga Pyramimonas parkeae, which harbors chloroplasts that are most closely related to the chloroplasts in photoautotrophic euglenids, both possessed only the MAT paralogue. We found both the MAT and MATX paralogues in two photoautotrophic species (Phacus orbicularis and Monomorphina pyrum). The significant conflict between eukaryotic phylogenies inferred from MATX and SSU rDNA data represents strong evidence that MATX paralogues have undergone horizontal gene transfer across the tree of eukaryotes. CONCLUSIONS: Our results suggest that MATX entered the euglenid lineage in a single horizontal gene transfer event that took place after the secondary endosymbiotic origin of the euglenid chloroplast. The origin of the MATX paralogue is unclear, and it cannot be excluded that it arose by a gene duplication event before the most recent common ancestor of eukaryotes.
- MeSH
- Chlorophyta enzymologie genetika fyziologie MeSH
- chloroplasty genetika MeSH
- Euglenida klasifikace enzymologie genetika fyziologie MeSH
- fylogeneze MeSH
- methioninadenosyltransferasa genetika MeSH
- molekulární evoluce * MeSH
- molekulární sekvence - údaje MeSH
- přenos genů horizontální MeSH
- protozoální proteiny genetika MeSH
- symbióza MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Many eukaryotic genes do not follow simple vertical inheritance. Elongation factor 1α (EF-1α) and methionine adenosyl transferase (MAT) are enzymes with complicated evolutionary histories and, interestingly, the two cases have several features in common. These essential enzymes occur as two relatively divergent paralogs (EF-1α/EFL, MAT/MATX) that have patchy distributions in eukaryotic lineages that are nearly mutually exclusive. To explain such distributions, we must invoke either multiple eukaryote-to-eukaryote horizontal gene transfers (HGTs) followed by functional replacement or presence of both paralogs in the common ancestor followed by long-term coexistence and differential losses in various eukaryotic lineages. To understand the evolution of these paralogs, we have performed in vivo experiments in Trypanosoma brucei addressing the consequences of long-term coexpression and functional replacement. In the first experiment of its kind, we have demonstrated that EF-1α and MAT can be simultaneously expressed with EFL and MATX, respectively, without affecting the growth of the flagellates. After the endogenous MAT or EF-1α was downregulated by RNA interference, MATX immediately substituted for its paralog, whereas EFL was not able to substitute for EF-1α, leading to mortality. We conclude that MATX is naturally capable of evolving patchy paralog distribution via HGTs and/or long- term coexpression and differential losses. The capability of EFL to spread by HGT is lower and so the patchy distribution of EF-1α/EFL paralogs was probably shaped mainly by deep paralogy followed by long-term coexistence and differential losses.
- MeSH
- biologická evoluce MeSH
- elongační faktor 1 genetika metabolismus MeSH
- genetická transkripce MeSH
- messenger RNA genetika MeSH
- methioninadenosyltransferasa genetika metabolismus MeSH
- přenos genů horizontální MeSH
- proliferace buněk MeSH
- regulace genové exprese MeSH
- RNA interference MeSH
- Trypanosoma brucei brucei genetika metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH