Biology subjects

Carney, T. D.

Publications and source records attributed to Carney, T. D..

4 recordsLinked to original sources

bioRxiv2024

Tumor suppressor miR-317 and lncRNA Peony are expressed from a polycistronic non-coding RNA locus that regulates germline differentiation and testis morphology

The impact of non-coding RNAs on stem cell biology and differentiation processes is an important and incompletely understood area of research. Using the testes of Drosophila melanogaster as a valuable system for investigating these processes, we identified a polycistronic locus from which two non-coding transcripts, miR-317 and the long non-coding RNA (lncRNA) Peony, are produced, with alternative polyadenylation implicated in regulation of their differential expression levels. We report here that each transcript has a distinct role in Drosophila testes; the increased expression of Peony results in the disruption of the muscle sheath covering the testis, and the absence of miR-317 leads to the emergence of germ-cell tumors in developing flies. The deficiency of miR-317 increases Notch signaling activity in somatic cyst cells, upregulates multiple predicted targets of miR-317, and drives germline tumorigenesis. Our findings establish miR-317 as a tumor suppressor controlling Notch signaling strength and uncover alternative polyadenylation as an unrecognized mechanism governing miRNA expression.

molecular biology↗

bioRxiv2023

The Drosophila MIC10 orthologue has a propensity to polymerize into cristae-shaping filaments

Mitochondria are essential eukaryotic double-membrane organelles. The convoluted mitochondrial inner membrane forms highly organized invaginations, termed cristae, which are crucial for energy metabolism. Cristae formation requires MICOS, a conserved hetero-oligomeric inner membrane complex. The MICOS core subunit MIC10 is a small transmembrane protein that oligomerizes through highly conserved glycine-rich motifs to control cristae formation. Sequence alignments show that D. melanogaster exhibits three MIC10-like proteins with different tissue-specific expression patterns. Here, we show that the ubiquitously expressed Dmel_CG41128/MINOS1b/DmMIC10b is the major MIC10 orthologue in flies. Loss of DmMIC10b disturbs cristae architecture of mitochondria and reduces the life-span and fertility of flies. Moreover, using fluorescence nanoscopy and electron tomography, we demonstrate that despite its high similarity to the MIC10 proteins from yeast and humans, DmMIC10b exhibits the unique ability to polymerize into elongated filaments upon overexpression. DmMIC10b filaments form bundles which accumulate in the intermembrane space and alter the shape of mitochondrial cristae membranes. We show that the formation of the filaments relies on conserved glycine and cysteine residues and is suppressed by co-expression of other MICOS proteins. Thereby, our findings provide new insights into the regulation of MICOS in flies.

cell biology↗

bioRxiv2022

Signaling through the Dystrophin Glycoprotein Complex affects the stress-dependent transcriptome in Drosophila

The Dystrophin Glycoprotein Complex (DGC) is a cell membrane-spanning complex that links the extracellular matrix with the intracellular cytoskeleton. Deficiencies in the DGC in humans cause muscular dystrophies (MDs), a group of inherited, incurable disorders associated with heterogeneous muscle, brain, and eye anomalies. To advance disease diagnostics and develop new treatment strategies, it is essential to understand the genetic pathways that are perturbed by DGC mutations and the mechanisms underlying these pathologies. Stresses such as nutrient deprivation and aging cause a reduction of muscle mass can be exacerbated by a reduced content of the DGC in membranes, whose integrity is vital for muscle health and function. This illustrates that the DGC plays a role in stress-response pathways. Therefore, it is important to investigate the influence of stress not only on healthy individuals but also on the wellbeing of MD patients. Moreover, the DGC has also emerged as an integral component in multiple signaling pathways, demonstrating an important yet poorly understood connection between intercellular forces and regulation of gene expression and illustrating the importance of understanding DGC-related transcriptional effects. Here, we utilize a Drosophila model to investigate the transcriptomic changes in mutants of four different DGC components under unstressed, temperature-stressed, and starvation-stressed conditions. Our analysis reveals a group of genes that exhibit DGC-dependent gene regulation. We identify large groups of genes that are differentially regulated in response to either temperature or starvation stress. Importantly, we also identify groups of genes with expression patterns dependent on the DGC signaling pathway for a proper stress response. This work reveals a novel function of the DGC in stress-response signaling. The view of the DGC as a regulatory unit involved in the stress response will give new insights into the etiology of symptoms of MDs and possible directions of symptomatic treatment and relief, and it will ultimately aid in a better understanding of DGC signaling and regulation under normal and stress conditions.

systems biology↗

bioRxiv2020

Tissue-specific regulation of translational readthrough tunes functions of the Traffic Jam transcription factor

Translational readthrough (TR) occurs when the ribosome decodes a stop codon as a sense codon, resulting in two protein isoforms synthesized from the same mRNA. TR is pervasive in eukaryotic organisms; however, its biological significance remains unclear. In this study, we quantify the TR potential of several candidate genes in Drosophila melanogaster and characterize the regulation of TR in the large Maf transcription factor Traffic jam (Tj). We used CRISPR/Cas9 generated mutant flies to show that the TR-generated Tj isoform is expressed in the nuclei of a subset of neural cells of the central nervous system and is excluded from the somatic cells of gonads, which express the short Tj isoform only. Translational control of TR is critical for preservation of neuronal integrity and maintenance of reproductive health. Fine-tuning of the gene regulatory functions of transcription factors by TR provides a new potential mechanism for cell-specific regulation of gene expression. HighlightsO_LITj undergoes tissue-specific TR in neural cells of the central nervous system. C_LIO_LIStrict control of TR is crucial for neuroprotection and maintenance of reproductive capacity. C_LIO_LITR selectively fine-tunes the gene regulatory functions of the transcription factor. C_LIO_LITR in Tj links transcription and translation of tissue-specific control of gene expression. C_LI O_FIG O_LINKSMALLFIG WIDTH=197 HEIGHT=200 SRC="FIGDIR/small/411694v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@1e6fb7dorg.highwire.dtl.DTLVardef@188d5c0org.highwire.dtl.DTLVardef@894173org.highwire.dtl.DTLVardef@127f4ae_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗