Biology subjects

Haussmann, I.

Publications and source records attributed to Haussmann, I..

6 recordsLinked to original sources

bioRxiv2025

Cap-adjacent 2'-O-ribose methylation of RNA in C. elegans is required for postembryonic growth and germline development in the presence of the decapping exonuclease EOL-1

Cap-adjacent 2-O-ribose methylation (cOMe) of the first two transcribed nucleotides of RNA polymerase II transcripts is a conserved feature in many eukaryotes. In mammals, these modifications are key to a transcript surveillance system that regulates the interferon response, but the broader functions of cOMe remain poorly understood. To understand the role of cOMe in C. elegans, we functionally characterised the methyltransferases (CMTR-1 and CMTR-2) responsible for installing these modifications. These enzymes have distinct expression patterns, protein interaction partners, and loss of function phenotypes. Loss of CMTR-1 causes dramatic reductions in cOMe, impaired growth and sterility. In contrast, animals lacking CMTR-2 are superficially wild-type, though CMTR-2 loss enhances the severity of the cmtr-1 mutant phenotype. Depletion of CMTR-1 causes downregulation of transcripts associated with germline sex determination and upregulation of those involved in the intracellular pathogen response (IPR). We show that absence of the decapping exonuclease, EOL-1, an IPR component, completely suppresses the sterility and growth defects caused of loss of CMTR-1, suggesting that EOL-1 degrades cellular transcripts lacking cOMe. Our work shows the physiological relevance of cOMe in protecting transcripts from decapping exonucleases, raising the possibility that cOMe plays a role in RNA-mediated immune surveillance beyond the vertebrates. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=79 SRC="FIGDIR/small/638824v2_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@1cd906dorg.highwire.dtl.DTLVardef@c4e922org.highwire.dtl.DTLVardef@1a5c2dborg.highwire.dtl.DTLVardef@19be5d8_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2023

Memory consolidation in honey bees is enhanced by down-regulation of Down Syndrome Cell Adhesion Molecule and changes its alternative splicing

Down syndrome cell adhesion molecule (Dscam) gene encodes a cell adhesion molecule required for neuronal wiring. A remarkable feature of invertebrate Dscam is massive alternative splicing generating thousands of different isoforms from three variable clusters of alternative exons. Dscam expression and diversity arising from alternative splicing have been studied during development, but whether they exert functions in differentiated brains has not been determined. Here, using honey bees, we find that Dscam expression is critically linked to memory retention as reducing expression by RNAi enhances memory after reward learning in adult worker bees. Moreover, alternative splicing of Dscam is altered in all three variable clusters after learning. Since identical Dscam isoforms engage in homophilic interactions, these results suggest a mechanism to alter inclusion of variable exons during memory consolidation to modify neuronal connections for memory retention.

neuroscience↗

bioRxiv2021

Dynamically expressed ELAV is required for learning and memory in bees

Changes in gene expression are a hallmark of learning and memory consolidation. Little is known about how alternative mRNA processing, particularly abundant in neuron-specific genes, contributes to these processes. Prototype RNA binding proteins of the neuronally expressed ELAV/Hu family are candidates for roles in learning and memory, but their capacity to cross-regulate and take over each others functions complicate substantiation of such links. Therefore, we focused on honey bees, which have only a single elav family gene. We find that honey bee elav contains a microexon, which is evolutionary conserved between invertebrates and humans. RNAi knockdown of elav demonstrates that ELAV is required for learning and memory in bees. Indicative of a role as immediate early gene, ELAV is dynamically expressed with altered alternative splicing and subcellular localization in mushroom bodies, but not in other brain parts. Expression and alternative splicing of elav change during memory consolidation illustrating an alternative mRNA processing program as part of a local gene expression response underlying memory formation. Although the honey bee genome encodes only a single elav gene, functional diversification is achieved by alternative splicing.

molecular biology↗

bioRxiv2021

CMTr cap-adjacent 2`-O-ribose mRNA methyltransferases are required for reward learning and mRNA localization to synapses

Cap-adjacent nucleotides of animal, protist and viral mRNAs can be dynamically O-methylated at the 2 position of the ribose (cOMe). The functions of cOMe in animals, however, remain unknown. Here we show that the two cap methyltransferases (CMTr1 and CMTr2) of Drosophila can methylate the ribose of the first nucleotide in mRNA. Double-mutant flies lack cOMe but are viable. Consistent with prominent neuronal expression, they have a reward learning defect that can be rescued by conditional expression in mushroom body neurons before training. Among CMTr targets are cell adhesion and signaling molecules relevant for learning and cOMe is required for local translation of mRNAs at synapses. Hence, our study reveals a mechanism to co-transcriptionally prime mRNAs by cOMe for localized protein synthesis at synapses.

molecular biology↗

bioRxiv2019

Channel nuclear pore protein 54 directs sexual differentiation and neuronal wiring required for female reproductive behaviors in Drosophila

The post-mating response induced by male-derived sex-peptide in Drosophila females is a well-established model to elucidate how complex innate behaviors are hard-wired into the brain. Here, we found that the channel nuclear pore protein Nup54 gene is essential for the sex-peptide response as viable mutant alleles do not lay eggs and reduce receptivity upon sex-peptide exposure. Nup54 directs correct wiring of few adult brain neurons that express pickpocket and are required for egg laying, but channel Nups also mediate sexual differentiation and male X-chromosome dosage compensation. Consistent with links of Nups to speciation, the Nup54 promoter is a hot spot for rapid evolution and promoter variants alter expression in transgenes. These results implicate altered expression of Nup54 to the onset of speciation processes leading to changes in neuronal wiring and sexual differentiation as a response to sexual conflict arising from male-derived SP to direct the female post-mating response.

genetics↗

bioRxiv2019

Srrm234, but not canonical SR and hnRNP proteins drive inclusion of Dscam exon 9 variable exons

Alternative splicing of pre-mRNA is a major mechanism to diversify protein functionality in metazoans from a limited number of genes. In the Drosophila melanogaster Down Syndrome Cell Adhesion Molecule (Dscam) important for neuronal wiring up to 38,016 isoforms can be generated by mutually exclusive alternative splicing in four clusters of variable exons. However, it is not understood how a specific exon is chosen from the many variables and how variable exons are prevented from being spliced together. A main role in the regulation of Dscam alternative splicing has been attributed to RNA binding proteins, but how they impact on exon selection is not well understood. Serine-arginine-rich (SR) proteins and hnRNP proteins are the two main types of RNA binding proteins with major roles in exon definition and splice site selection. Here, we analyzed the role of SR and hnRNP proteins in Dscam exon 9 alternative splicing in mutant Drosophila melanogaster embryos because of their essential function for development. Strikingly, loss or overexpression of canonical SR and hnRNP proteins even when multiple proteins are depleted together, does not affect Dscam alternative exon selection very dramatically. Conversely, non-canonical SR protein Serine-arginine repetitive matrix 2/3/4 (Srrm234) is a main determinant of exon inclusion in Dscam exon 9 cluster. Since long-range base-pairings are absent in the exon 9 cluster, our data argue for a small complement of regulatory factors as main determinants of exon inclusion in the Dscam exon 9 cluster.

molecular biology↗