Our research focuses on functional and evolutionary aspects of small RNA pathways. This involves the development of bioinformatics tools for analysis of high-throughput sequencing data to characterize different classes of small RNAs.

Background: Jumping Genes     show Background: Small RNAs     show

- How secondary structure influences small RNA pathways
Transposable elements in the tree shrew are targeted not only by piRNAs but also by smaller RNAs resembling typical features of siRNAs. Comprehensive bioinformatic analyses showed that piRNAs preferentially target transposon transcripts at sites that do not form foldback structures and thus remain accessible for guiding piRNAs. In contrast, sites that avoid piRNA targeting owing to strong secundary structures are processed by Dicer, an enzyme that recognizes double-stranded RNA (Rosenkranz et al. 2015, RNA 21(5):911-922).

piRNAs and siRNAs target transposon transcripts

- How temperature influences small RNA pathways
Altered ambient temperature induces drastic, but reversible changes in sequence composition and total abundance of both, miRNA- and piRNA populations in Drosophila. Regarding miRNAs, we can distinguish between miRNAs with higher abundance at Hyper-Optimal Temperature (29C, HOT-miRNAs) and miRNAs with higher abundance at Near-Optimal Temperature (18C, NOT-miRNAs). Further, the expression of temperature-responsive miRNAs and their predicted target transcripts correlates inversely, suggesting that temperature-responsive miRNAs drive adaptation to different ambient temperatures on the transcriptome level.
In addition, altered temperature not only affects miRNA expression but also influences piRNA biogenesis. We observed significantly increased ping-pong processing at 29C which is presumably driven by dissolved RNA secondary structures at higher temperatures, uncovering target sites that are not accessible at low temperatures. (Fast et al. 2017, RNA 23(9):1352-1364).

temperature-responsive miRNAs

- Near-neutral sequence evolution of piRNA clusters and piRNAs
piRNA clusters do not evolve uniformely. Instead, we can observe different conservation patterns within the same piRNA clusters. Residues that are overrepresented in tree shrew (Tupaia belangeri) testis piRNA transcriptomes show stronger sequence conservation, whereas piRNA coding residues in general show only very weak sequence conservation . In contrast, regulatory elements such as A-Myb transcription factor binding sites exhibit stronger sequence conservation, showing that the ability of a genomic locus to produce piRNAs is more important than preserving primary sequences of piRNAs (Rosenkranz et al. 2015, RNA 21(5):911-922).

- Conservation of piRNA-mediated gene regulatory function
While in flys piRNAs are enriched for transposon sequences, the majority of mammalian pachytene piRNAs matches single-copy sequences. This raised the question of whether the Piwi/piRNA system is involved in functions beyond transposon silencing. Our in-deep characterization of the porcine testis piRNA transcriptome provided evidence for a processing of protein-coding transcripts within the piRNA ping-pong cycle. Remarkably, orthologous genes (but not simply highly expressed genes) are targeted by piRNAs accross different mammalian species pointing towards a conserved function of the Piwi/piRNA pathway in post-transcriptional gene regulation in mammals (Gebert et al. 2015, PLoS ONE 10(5):e0124860).

piRNAs target transcripts of protein-coding genes

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