Mobility of transposable elements (TEs) frequently leads to insertional mutations in functional DNA regions. In the potentially immortal germline, TEs are effectively suppressed by the Piwi-piRNA pathway. However, in the genomes of ageing somatic cells lacking the effects of the pathway, TEs become increasingly mobile during the adult lifespan, and their activity is associated with genomic instability. Whether the progressively increasing mobilization of TEs is a cause or a consequence of ageing remains a fundamental problem in biology. Here we show that in the nematode Caenorhabditis elegans, the downregulation of active TE families extends lifespan. Ectopic activation of Piwi proteins in the soma also promotes longevity. Furthermore, DNA N6-adenine methylation at TE stretches gradually rises with age, and this epigenetic modification elevates their transcription as the animal ages. These results indicate that TEs represent a novel genetic determinant of ageing, and that N6-adenine methylation plays a pivotal role in ageing control.
25 November 2023 in Journal of Experimental Botany
Strigolactones and ABA are apocarotenoid-derived plant hormones. Their biosynthesis starts with the conversion of trans-carotenes into cis forms, which serve as direct precursors. Iron-containing DWARF27 isomerases were shown to catalyse or contribute to the trans/cis conversions of these precursor molecules. D27 converts trans-β-carotene into 9-cis-β-carotene which is the first committed step in strigolactone biosynthesis. Recent studies found that its paralog, D27-LIKE1 also catalyses this conversion. A crucial step in ABA biosynthesis is the oxidative cleavage of 9-cis-violaxanthin and/or 9-cis-neoxanthin which are formed from their trans isomers by unknown isomerases. Several lines of evidence point out that D27-like proteins directly, or indirectly contribute to 9-cis-violaxanthin conversion and eventually, ABA biosynthesis. Apparently, the diversity of D27-like enzymatic activity is essential for the optimization of cis/trans ratios, and hence, act to maintain apocarotenoid precursor pools. In this review we discuss the functional divergence and redundancy of D27 paralogs and their potential direct contribution to ABA precursor biosynthesis. We provide updates on their gene expression regulation and alleged Fe-S cluster binding feature. Finally, we conclude that the functional divergence of these paralogs is not fully understood and we give an outlook on potential directions in research.
N6-methyladenine (6mA) in the DNA is a conserved epigenetic mark with various cellular, physiological and developmental functions. Although the presence of 6mA was discovered a few years ago in the nuclear genome of distantly related animal taxa and just recently in mammalian mitochondrial DNA (mtDNA), accumulating evidence at present seriously questions the presence of N6-adenine methylation in these genetic systems, attributing it to methodological errors. In this paper, we present a reliable, PCR-based method to determine accurately the relative 6mA levels in the mtDNA of Caenorhabditis elegans, Drosophila melanogaster and dogs, and show that these levels gradually increase with age. Furthermore, daf-2(−)-mutant worms, which are defective for insulin/IGF-1 (insulin-like growth factor) signaling and live twice as long as the wild type, display a half rate at which 6mA progressively accumulates in the mtDNA as compared to normal values. Together, these results suggest a fundamental role for mtDNA N6-adenine methylation in aging and reveal an efficient diagnostic technique to determine age using DNA.