Regulation of transposable elements by DNA modifications

Hung

et al. 2019

Preprint

Self Cite

The Arabidopsis DEMETER (DME) DNA glycosylase demethylates the maternal genome in the central cell prior to fertilization, and is essential for seed viability. DME preferentially targets small transposons that flank coding genes, influencing their expression and initiating plant gene imprinting. DME also targets intergenic and heterochromatic regions, and how it is recruited to these differing chromatin landscapes is unknown. The C--terminal DME catalytic core consists of three conserved regions required for catalysis in vitro. We show that the catalytic core of DME guides active demethylation at endogenous targets, rescuing the developmental and genomic hypermethylation phenotypes of DME mutants. However, without the N--terminus, heterochromatin demethylation is significantly impeded, and abundant CG--methylated genic sequences are ectopically demethylated. We used comparative analysis to reveal that the conserved DME N--terminal domains are only present in the flowering plants, whereas the domain architecture of DME--like proteins in non--vascular plants mainly resembles the catalytic core, suggesting that it might represent the ancestral form of the 5mC DNA glycosylase found in all plant lineages. We propose a bipartite model for DME protein action and suggest that the DME N--terminus was acquired late during land plant evolution to improve specificity and facilitate demethylation at heterochromatin targets.

Section: Introductionmentioning

confidence: 99%

The Catalytic Core of DEMETER Guides Active DNA Demethylation in Arabidopsis

Hung

et al. 2019

Preprint

Self Cite

“…As previously hypothesized (26), plant and animal retrozymes would follow a similar life cycle for their spreading throughout genomes as non-autonomous retroelements. Both types of retrozymes express and accumulate at high levels in either somatic or germinal tissues of any organism analysed, an atypical behaviour for retroelements, which are generally inactive in most cell types and conditions (44)(45)(46). But eukaryotic retrozyme repeats are intensively transcribed to produce oligomeric RNAs, which self-process through their HHR motifs.…”

Section: Discussionmentioning

confidence: 99%

Small circRNAs with self-cleaving ribozymes are frequently expressed in metazoan transcriptomes

Cervera

Peña

2019

Preprint

Ribozymes are catalytic RNAs present in modern genomes but considered as remnants of a prebiotic RNA world. The paradigmatic hammerhead ribozyme (HHR) is a small self-cleaving motif widespread from bacterial to human genomes. Here, we report that most of the classical type I HHRs frequently found in the genomes of diverse animals are contained within a novel family of non-autonomous non-LTR retrotransposons. These retroelements are expressed as abundant linear and circular RNAs of ~170-400 nt in different animal tissues. In vitro analyses confirm an efficient self-cleavage of the HHRs harboured in invertebrate retrozymes, whereas those in retrozymes of vertebrates, such as the axolotl, require to act as dimeric motifs to reach higher self-cleavage rates. Ligation assays of retrozyme RNAs with a protein ligase versus HHR self-ligation indicate that, most likely, tRNA ligases and not the ribozymes are involved in the step of RNA circularization. Altogether, these results confirm the existence of a new and conserved pathway in animals and, likely, in eukaryotes in general, for the efficient biosynthesis of RNA circles through small ribozymes, which will allow the development of biotechnological tools in the emerging field of circRNAs.

“…m5C at CpG islands in the promoters represses gene expression [3]. m5C is also important for the repression of transposable elements [6].…”

Section: Dna and Rna Modificationsmentioning

confidence: 99%

Recent advances in the detection of base modifications using the Nanopore sequencer

Seki

2019

J Hum Genet

107

DNA and RNA modifications have important functions, including the regulation of gene expression. Existing methods based on short-read sequencing for the detection of modifications show difficulty in determining the modification patterns of single chromosomes or an entire transcript sequence. Furthermore, the kinds of modifications for which detection methods are available are very limited. The Nanopore sequencer is a single-molecule, long-read sequencer that can directly sequence RNA as well as DNA. Moreover, the Nanopore sequencer detects modifications on long DNA and RNA molecules. In this review, we mainly focus on base modification detection in the DNA and RNA of mammals using the Nanopore sequencer. We summarize current studies of modifications using the Nanopore sequencer, detection tools using statistical tests or machine learning, and applications of this technology, such as analyses of open chromatin, DNA replication, and RNA metabolism.