@article{ThoelkenThammErbacheretal.2019,
  author    = {Th{\"o}lken, Clemens and Thamm, Markus and Erbacher, Christoph and Lechner, Marcus},
  title     = {Sequence and structural properties of circular RNAs in the brain of nurse and forager honeybees (Apis mellifera)},
  series = {BMC Genomics},
  volume    = {20},
  journal   = {BMC Genomics},
  doi       = {10.1186/s12864-018-5402-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241302},
  year      = {2019},
  abstract  = {Background The honeybee (Apis mellifera) represents a model organism for social insects displaying behavioral plasticity. This is reflected by an age-dependent task allocation. The most protruding tasks are performed by young nurse bees and older forager bees that take care of the brood inside the hive and collect food from outside the hive, respectively. The molecular mechanism leading to the transition from nurse bees to foragers is currently under intense research. Circular RNAs, however, were not considered in this context so far. As of today, this group of non-coding RNAs was only known to exist in two other insects, Drosophila melanogaster and Bombyx mori. Here we complement the state of circular RNA research with the first characterization in a social insect. Results We identified numerous circular RNAs in the brain of A. mellifera nurse bees and forager bees using RNA-Seq with exonuclease enrichment. Presence and circularity were verified for the most abundant representatives. Back-splicing in honeybee occurs further towards the end of transcripts and in transcripts with a high number of exons. The occurrence of circularized exons is correlated with length and CpG-content of their flanking introns. The latter coincides with increased DNA-methylation in the respective loci. For two prominent circular RNAs the abundance in worker bee brains was quantified in TaqMan assays. In line with previous findings of circular RNAs in Drosophila, circAmrsmep2 accumulates with increasing age of the insect. In contrast, the levels of circAmrad appear age-independent and correlate with the bee's task. Its parental gene is related to amnesia-resistant memory. Conclusions We provide the first characterization of circRNAs in a social insect. Many of the RNAs identified here show homologies to circular RNAs found in Drosophila and Bombyx, indicating that circular RNAs are a common feature among insects. We find that exon circularization is correlated to DNA-methylation at the flanking introns. The levels of circAmrad suggest a task-dependent abundance that is decoupled from age. Moreover, a GO term analysis shows an enrichment of task-related functions. We conclude that circular RNAs could be relevant for task allocation in honeybee and should be investigated further in this context.},
  language  = {en}
}
@phdthesis{Hillebrand2013,
  author    = {Hillebrand, Frank},
  title     = {Der Einfluss des PI3-Kinase Signalwegs auf die Regulation des alternativen HIV-1 pr{\"a}-mRNA Spleißens},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-76914},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {In der vorliegenden Arbeit wurden ausgehend von HIV-1 basierten Minigenkonstrukten und der proviralen NL4-3 DNA die Einfl{\"u}sse der PI3K Signalwegmodulation auf das alternative Spleißen der HIV-1 pr{\"a}-mRNA sowie auf die Virus Replikation untersucht. Mittels RT-PCR Analysen konnte gezeigt werden, dass die PI3K Inhibition im Falle der HIV-1 basierten Minigenkonstrukte in einer erh{\"o}hten Abundanz ungespleißter bzw. intronhaltiger mRNAs resultierte, w{\"a}hrend im Kontext des Virus die Induktion alternativer Tat Transkriptvarianten nachgewiesen werden konnte. Als Folge der Inhibition des PI3K Signalwegs kam es zu einem vermehrten Einschluss der HIV-1 Leader Exone2/2b und 3. Da der Einschluss dieser Exone durch die hnRNP A/B- und F/H-abh{\"a}ngigen Silencer Elemente ESSV und GI2-1 negativ reguliert wird, wurde vermutet, dass die PI3K Inhibition mit der Funktionalit{\"a}t dieser spleißregulatorischen Aktivit{\"a}t interferiert. Unterst{\"u}tzt wurde diese Hypothese durch Replikationsexperimente mit ESSV und GI2-1 Mutanten in Gegenwart und Abwesenheit des PI3K-Inhibitors. Zus{\"a}tzlich wurde auch der Einfluss des Inhibitors unter {\"U}berexpressionsbedingungen von hnRNP H auf das alternative HIV-1 Spleißen analysiert. In dieser Arbeit konnte ebenfalls gezeigt werden, dass die PI3K Inhibition ein ver{\"a}ndertes hnRNP H Spleißmuster bedingt sowie die SR-Protein Phosphorylierung und Expression beeinflusst. Des Weiteren war es im Verlauf der vorliegenden Arbeit m{\"o}glich, eine Interferenz der PI3K Modulation mit der Virus Replikation nachzuweisen. Die {\"U}berexpression der aktivierten Akt-Kinase lies hier nur eine sehr geringe Virus Produktion zu w{\"a}hrend die PI3K Inhibition diese auf ca. die H{\"a}lfte reduzierte. Weiterf{\"u}hrende Experimente zeigten, dass die {\"U}berexpression der aktivierten Akt-Kinase den nuklearen Export Rev-abh{\"a}ngiger HIV-1 mRNAs zu blockieren scheint. Dar{\"u}ber hinaus beeinflusste die PI3K Inhibition neben dem alternativen HIV-1 Spleißen auch die virale Transkription sowie die zellul{\"a}re Translation. Zusammen k{\"o}nnten diese Effekte die reduzierte virale Replikation erkl{\"a}ren. Der PI3K Signalweg spielt somit eine zentrale Rolle bei dem alternativen HIV-1 Spleißen und der viralen Replikation und bietet so die M{\"o}glichkeit der Entwicklung neuer Ans{\"a}tze einer antiviralen Therapie.  },
  subject      = {RNS-Spleißen},
  language  = {de}
}
@article{RiedelMofoloAvotaetal.2013,
  author    = {Riedel, Alice and Mofolo, Boitumelo and Avota, Elita and Schneider-Schaulies, Sibylle and Meintjes, Ayton and Mulder, Nicola and Kneitz, Susanne},
  title     = {Accumulation of Splice Variants and Transcripts in Response to PI3K Inhibition in T Cells},
  series = {PLoS ONE},
  volume    = {8},
  journal   = {PLoS ONE},
  number    = {2},
  doi       = {10.1371/journal.pone.0050695},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130335},
  pages     = {e50695},
  year      = {2013},
  abstract  = {Background Measles virus (MV) causes T cell suppression by interference with phosphatidylinositol-3-kinase (PI3K) activation. We previously found that this interference affected the activity of splice regulatory proteins and a T cell inhibitory protein isoform was produced from an alternatively spliced pre-mRNA. Hypothesis Differentially regulated and alternatively splice variant transcripts accumulating in response to PI3K abrogation in T cells potentially encode proteins involved in T cell silencing. Methods To test this hypothesis at the cellular level, we performed a Human Exon 1.0 ST Array on RNAs isolated from T cells stimulated only or stimulated after PI3K inhibition. We developed a simple algorithm based on a splicing index to detect genes that undergo alternative splicing (AS) or are differentially regulated (RG) upon T cell suppression. Results Applying our algorithm to the data, 9\% of the genes were assigned as AS, while only 3\% were attributed to RG. Though there are overlaps, AS and RG genes differed with regard to functional regulation, and were found to be enriched in different functional groups. AS genes targeted extracellular matrix (ECM)-receptor interaction and focal adhesion pathways, while RG genes were mainly enriched in cytokine-receptor interaction and Jak-STAT. When combined, AS/RG dependent alterations targeted pathways essential for T cell receptor signaling, cytoskeletal dynamics and cell cycle entry. Conclusions PI3K abrogation interferes with key T cell activation processes through both differential expression and alternative splicing, which together actively contribute to T cell suppression.},
  language  = {en}
}