@article{Essig2018,
author = {Essig, Katharina and Kronbeck, Nina and Guimaraes, Joao C and Lohs, Claudia and Schlundt, Andreas and Hoffmann, Anne and Behrens, Gesine and Brenner, Sven and Kowalska, Joanna and Lopez-Rodriguez, Cristina and Jemielity, Jacek and Holtmann, Helmut and Reiche, Kristin and Hackerm{\"u}ller, J{\"o}rg and Sattler, Michael and Zavolan, Mihaela and Heissmeyer, Vigo},
title = {Roquin targets mRNAs in a 3′-UTR-specific manner by different modes of regulation},
journal = {Nature Communications},
volume = {9},
number = {1},
pages = {2041-1723},
year = {2018},
doi = {10.1038/s41467-018-06184-3},
URL = {https://doi.org/10.1038/s41467-018-06184-3},
abstract = {{The RNA-binding proteins Roquin-1 and Roquin-2 redundantly control gene expression and cell-fate decisions. Here, we show that Roquin not only interacts with stem–loop structures, but also with a linear sequence element present in about half of its targets. Comprehensive analysis of a minimal response element of the Nfkbid 3′-UTR shows that six stem–loop structures cooperate to exert robust and profound post-transcriptional regulation. Only binding of multiple Roquin proteins to several stem–loops exerts full repression, which redundantly involved deadenylation and decapping, but also translational inhibition. Globally, most Roquin targets are regulated by mRNA decay, whereas a small subset, including the Nfat5 mRNA, with more binding sites in their 3′-UTRs, are also subject to translational inhibition. These findings provide insights into how the robustness and magnitude of Roquin-mediated regulation is encoded in complex cis-elements.}}
}


@article{Behrens_2018,
        author = {Behrens, Gesine and Winzen, Reinhard and Rehage, Nina and D{\"o}rrie, Anneke and Barsch, Monika and Hoffmann, Anne and Hackerm{\"u}ller, J{\"o}rg and Tiedje, Christopher and Heissmeyer, Vigo and Holtmann, Helmut},
        title = {A translational silencing function of MCPIP1/Regnase-1 specified by the target site context},
        journal = {Nucleic Acids Research},
        volume = {46},
        number = {8},
        pages = {4256-4270},
        year = {2018},
        doi = {10.1093/nar/gky106},
        URL = {http://dx.doi.org/10.1093/nar/gky106},
        eprint = {/oup/backfile/content_public/journal/nar/46/8/10.1093_nar_gky106/1/gky106.pdf},
        abstract = {{The expression of proteins during inflammatory and immune reactions is coordinated by post-transcriptional mechanisms. A particularly strong suppression of protein expression is exerted by a conserved translational silencing element (TSE) identified in the 3' UTR of NFKBIZ mRNA, which is among the targets of the RNA-binding proteins Roquin-1/2 and MCPIP1/Regnase-1. We present evidence that in the context of the TSE MCPIP1, so far known for its endonuclease activity toward mRNAs specified by distinct stem-loop (SL) structures, also suppresses translation. Overexpression of MCPIP1 silenced translation in a TSE-dependent manner and reduced ribosome occupancy of the mRNA. Correspondingly, MCPIP1 depletion alleviated silencing and increased polysomal association of the mRNA. Translationally silenced NFKBIZ or reporter mRNAs were mostly capped, polyadenylated and ribosome associated. Furthermore, MCPIP1 silenced also cap-independent, CrPV-IRES-dependent translation. This suggests that MCPIP1 suppresses a post-initiation step. The TSE is predicted to form five SL structures. SL4 and 5 resemble target structures reported for MCPIP1 and together were sufficient for MCPIP1 binding and mRNA destabilization. Translational silencing, however, required SL1-3 in addition. Thus the NFKBIZ TSE functions as an RNA element in which sequences adjacent to the site of interaction with MCPIP1 and dispensable for accelerated mRNA degradation extend the functional repertoire of MCPIP1 to translational silencing.}}
}

@article{Hoffmann_2018,
        author = {Hoffmann, Anne and Fallmann, J{\"o}rg and Vilardo, Elisa and M{\"o}rl, Mario and Stadler, Peter F. and Amman, Fabian},
        title = {Accurate mapping of tRNA reads},
        journal = {Bioinformatics},
        volume = {34},
        number = {7},
        pages = {1116-1124},
        year = {2018},
        doi = {10.1093/bioinformatics/btx756},
        URL = {http://dx.doi.org/10.1093/bioinformatics/btx756},
        eprint = {/oup/backfile/content_public/journal/bioinformatics/34/7/10.1093_bioinformatics_btx756/2/btx756.pdf},
	abstract = {{Motivation: Many repetitive DNA elements are transcribed at appreciable expression levels. Mapping the corresponding RNA sequencing reads back to a reference genome is notoriously difficult and error-prone task, however. This is in particular true if chemical modifications introduce systematic mismatches, while at the same time the genomic loci are only approximately identical, as in the case of tRNAs. Results: We therefore developed a dedicated mapping strategy to handle RNA-seq reads that map to tRNAs relying on a modified target genome in which known tRNA loci are masked and instead intronless tRNA precursor sequences are appended as artificial 'chromosomes'. In a first pass, reads that overlap the boundaries of mature tRNAs are extracted. In the second pass, the remaining reads are mapped to a tRNA-masked target that is augmented by representative mature tRNA sequences. Using both simulated and real life data we show that our best-practice workflow removes most of the mapping artefacts introduced by simpler mapping schemes and makes it possible to reliably identify many of chemical tRNA modifications in generic small RNA-seq data. Using simulated data the FDR is only 2%. We find compelling evidence for tissue specific differences of tRNA modification patterns. Availability and implementation: The workflow is available both as a bash script and as a Galaxy workflow from https://github.com/AnneHoffmann/tRNA-read-mapping.}}		
}

@Article{Rehage_2018,
        author = {Rehage, Nina and Davydova, Elena and Conrad, Christine and Behrens, Gesine and Maiser, Andreas and Stehklein, Jenny E. and Brenner, Sven and Klein, Juliane and Jeridi, Aicha and Hoffmann, Anne and Lee, Eunhae and Dianzani, Umberto and Willemsen, Rob and Feederle, Regina and Reiche, Kristin and Hackerm{\"u}ller, J{\"o}rg and Leonhardt, Heinrich and Sharma, Sonia and Niessing, Dierk and Heissmeyer, Vigo},
        year = {2018},
        title = {Binding of NUFIP2 to Roquin promotes recognition and regulation of ICOS mRNA},
        journal = {Nature Communications},
        pages = {299},
        volume = {9},
        issue = {1},
        abstract = {{The ubiquitously expressed RNA-binding proteins Roquin-1 and
Roquin-2 are essential for appropriate immune cell function and
postnatal survival of mice. Roquin proteins repress target mRNAs by
recognizing secondary structures in their 3'-UTRs and by inducing mRNA
decay. However, it is unknown if other cellular proteins contribute to
target control. To identify cofactors of Roquin, we used RNA
interference to screen ~1500 genes involved in RNA-binding or mRNA
degradation, and identified NUFIP2 as a cofactor of Roquin-induced mRNA
decay. NUFIP2 binds directly and with high affinity to Roquin, which
stabilizes NUFIP2 in cells. Post-transcriptional repression of human
ICOS by endogenous Roquin proteins requires two neighboring
non-canonical stem-loops in the ICOS 3'-UTR. This unconventional
cis-element as well as another tandem loop known to confer
Roquin-mediated regulation of the Ox40 3'-UTR, are bound cooperatively
by Roquin and NUFIP2. NUFIP2 therefore emerges as a cofactor that
contributes to mRNA target recognition by Roquin.}},
        url = {https://doi.org/10.1038/s41467-017-02582-1},
        doi = {10.1038/s41467-017-02582-1}
}

@Article{Berkemer_2017,
        author = {Berkemer, Sarah J. and Hoffmann, Anne and Murray, Cameron R. A. and Stadler, Peter F.},
        title = {{SMORE: Synteny Modulator of Repetitive Elements}},
        journal = {Life},
        volume = {7},
        year = {2017},
        number = {42},
        url = {http://www.mdpi.com/2075-1729/7/4/42},
        issn = {2075-1729},
        abstract = {{Several families of multicopy genes, such as transfer ribonucleic acids (tRNAs) and ribosomal RNAs (rRNAs), are subject to concerted evolution, an effect that keeps sequences of paralogous genes effectively identical. Under these circumstances, it is impossible to distinguish orthologs from paralogs on the basis of sequence similarity alone. Synteny, the preservation of relative genomic locations, however, also remains informative for the disambiguation of evolutionary relationships in this situation. In this contribution, we describe an automatic pipeline for the evolutionary analysis of such cases that use genome-wide alignments as a starting point to assign orthology relationships determined by synteny. The evolution of tRNAs in primates as well as the history of the Y RNA family in vertebrates and nematodes are used to showcase the method. The pipeline is freely available.}},
        doi = {10.3390/life7040042}
}

@Article{Velandia-Huerto2016,
        author = {Velandia-Huerto, Cristian A. and Berkemer, Sarah J. and Hoffmann, Anne and Retzlaff, Nancy and Romero Marroqu{\'i}n, Liliana C. and Hern{\'a}ndez-Rosales, Maribel and Stadler, Peter F. and Berm{\'u}dez-Santana, Clara I.},
        title = {{Orthologs, turn-over, and remolding of tRNAs in primates and fruit flies}},
        journal = {BMC Genomics},
        year = {2016},
        volume = {17},
        number = {1},
        pages = {617},
        abstract = {{Transfer RNAs (tRNAs) are ubiquitous in all living organism. They implement the genetic code so that most genomes contain distinct tRNAs for almost all 61 codons. They behave similar to mobile elements and proliferate in genomes spawning both local and non-local copies. Most tRNA families are therefore typically present as multicopy genes. The members of the individual tRNA families evolve under concerted or rapid birth-death evolution, so that paralogous copies maintain almost identical sequences over long evolutionary time-scales. To a good approximation these are functionally equivalent. Individual tRNA copies thus are evolutionary unstable and easily turn into pseudogenes and disappear. This leads to a rapid turnover of tRNAs and often large differences in the tRNA complements of closely related species. Since tRNA paralogs are not distinguished by sequence, common methods cannot not be used to establish orthology between tRNA genes.}},
        issn = {1471-2164},
        doi = {10.1186/s12864-016-2927-4},
        url = {https://doi.org/10.1186/s12864-016-2927-4}
}

@phdthesis{Hoffmann_2015,
        address = {Leipzig, Germany},
        type = {Master's {{Thesis}}},
        title = {{RNA secondary structure determinants of Roquin - RNA interactions}},
        copyright = {All rights reserved},
        abstract = {{Translational repression and mRNA degradation mediate cellular response to environmental changes and are proposed as essential steps of gene expression control. Post-transcriptional gene regulation is often linked to human diseases and involves RNA-binding proteins which recognize structured sequence motifs in 3'UTRs. The RNA-binding protein Roquin is determined as a key regulator in the maintenance of immunological tolerance and prevention of autoimmune diseases. The post-transcriptional control of inflammatory gene expression by Roquin is not yet fully understood. During this work we were able to show that recently published and predicted putative Roquin-binding sites are structurally rather than sequentially conserved among vertebrates confirming Roquin-depended regulation of relaxed motifs. Our calculated realization probabilities of single or combined Roquin-binding sites in the thermodynamic equilibrium ensemble predicted simultaneous interactions or functionality exchange between certain motifs. We demonstrated that Roquin binding sites are structurally similar in different transcripts and we divided the motifs into two structural classes. Each class was characteristic either for tri- or hexaloop hairpin structures. We suspect that Roquin shows a larger tendency to bind to triloop motifs when regulating mRNA degradation and to hexaloop motifs when initiating translational repression, respectively.}},
        school = {Martin-Luther University of Halle (Saale) and Helmholz Centre for Environmental Research (UFZ)},
  author = {Hoffmann, Anne},
  year = {2015}
}


@phdthesis{Hoffmann_2012,
        address = {Halle (Saale), Germany},
        type = {BAchelor's {{Thesis}}},
	title = {Molecular genetic characterization of phosphorylatable amino acids of the histone demethylase LSD1 in Drosophila melanogaster},
	copyright = {All rights reserved},
        school = {Martin-Luther University of Halle (Salle)},
  	author = {Hoffmann, Anne},
 	year = {2012}
}