Biology subjects

Rollins, J. A.

Publications and source records attributed to Rollins, J. A..

5 recordsLinked to original sources

bioRxiv2025

Modified tau leads to neuronal and global ribosome dysfunction in C. elegans model of tauopathy

Alzheimers disease (AD) is a neurodegenerative disease characterized by an early loss of memory formation which requires protein synthesis. Tau is an intrinsically disordered protein and is subject to extensive post-translational modifications (PTMs). Some PTMs have been shown to alter localization of tau and allow tau to disrupt protein translation. Protein interactome studies indicate that tau might interact with ribosomal proteins. Therefore, we hypothesized that tau is causing ribosomal dysfunction as an early event and this interaction is dependent on taus PTMs. To test this, we used a C. elegans strain expressing single copy insertion of human tau as well as two of the most frequent modified versions of tau in mechanosensory neurons. With our assay to measure translation, we showed that in our T231 phosphorylation mimetic strain, there was a significant decrease in neuronal translation. This mimetic strain also showed a significant decrease in median lifespan and locomotion. Unexpectedly, in all our Tau-expressing strains, we detected a significant decrease in whole worm translation, suggesting a possible role of tau to influence translation in other tissues in worm. Our in vitro, in vivo and ex vivo efforts to demonstrate tau-ribosome association via fluorescent polysome profiling have shown that there is no direct association between tau and the ribosome. Ribosome dysfunction caused by modified tau could be an early event in AD pathology before the pathological hallmarks appear.

neuroscience↗

bioRxiv2025

Integration of a neuronal RNAseq dataset with the draft Gryllus bimaculatus transcriptome refines gene predictions and highlights potential systematic response to injury

The cricket Gryllus bimaculatus presents a compelling model for investigating neuroplasticity due to its unusual capability of adult structural reorganization. The molecular pathways underlying these changes are entirely unknown. Here, we reanalyzed RNAseq data, drawn from deafferented neuronal tissue one, three, and seven days post-injury, that was previously used to assemble a de novo transcriptome. In this current analysis, we aligned our original RNAseq data to the publicly available G. bimaculatus draft genome, and used the resulting alignments to refine and update the existing annotations. We identified over 10,000 missing genes and reported a measurable improvement in BUSCO scores. These updated annotations were then used as the basis for a DESeq2 differential expression analysis and subsequent functional enrichment analysis to further explore the potential molecular basis of this compensatory anatomical plasticity. Days one and three showed the largest post-deafferentation expression differences. Overall, more transcripts were upregulated rather than downregulated. Protein-protein interactions enriched for G-protein-related signaling, hormone metabolism, and membrane dynamics were evident. Changes in expression of factors related to small GTPases and nervous system development were particularly intriguing. We also identified a surprising enrichment of GO terms related to muscle contraction in this neuronal-specific transcriptome. Identifying these and other differentially regulated transcripts can be used to design hypotheses around well-conserved molecular mechanisms that may be involved in this unique example of adult structural plasticity in the cricket.

neuroscience↗

bioRxiv2020

The infection cushion: a fungal weapon of plant-biomass destruction

O_LIGrey mold disease affects fruits, vegetables and ornamental plants around the world, causing considerable losses every year. Its causing agent, the necrotrophic fungus Botrytis cinerea, produces infection cushions (IC) that are compound appressorial structures dedicated to the penetration of the plant tissues. C_LIO_LIA microarray analysis was performed to identify genes up-regulated in mature IC. The expression data were supported by RT-qPCR analysis performed in vitro and in planta, proteomic analysis of the IC secretome and mutagenesis of two candidate genes. C_LIO_LI1,231 up-regulated genes and 79 up-accumulated proteins were identified. They highlight a secretion of ROS, secondary metabolites including phytotoxins, and proteins involved in virulence: proteases, plant cell wall degrading enzymes and necrosis inducers. The role in pathogenesis was confirmed for two up-regulated fasciclin genes. DHN-melanin pathway and chitin deacetylases genes are up-regulated and the conversion of chitin into chitosan was confirmed by differential staining of the IC cell wall. In addition, up-regulation of sugar transport and sugar catabolism encoding genes was found. C_LIO_LIThese results support a role for the B. cinerea IC in plant penetration and suggest other unexpected roles for this fungal organ, in camouflage, necrotrophy or nutrition of the pathogen. C_LI

microbiology↗

bioRxiv2020

The ribosomal RNA m5C methyltransferase NSUN-1 modulates healthspan and oogenesis in Caenorhabditis elegans

Our knowledge about the repertoire of ribosomal RNA modifications and the enzymes responsible for installing them is constantly expanding. Previously, we reported that NSUN-5 is responsible for depositing m5C at position C2381 on the 26S rRNA in Caenorhabditis elegans. Here, we show that NSUN-1 is writing the second known 26S rRNA m5C at position C2982. Depletion of nsun-1 or nsun-5 improved locomotion at midlife and resistance against heat stress, however, only soma-specific knockdown of nsun-1 extended lifespan. Moreover, soma-specific knockdown of nsun-1 reduced body size and impaired fecundity, suggesting non-cell-autonomous effects. While ribosome biogenesis and global protein synthesis were unaffected by nsun-1 depletion, translation of specific mRNAs was remodelled leading to reduced production of collagens, loss of structural integrity of the cuticle and impaired barrier function. We conclude that loss of a single enzyme required for rRNA methylation has profound and highly specific effects on organismal physiology.

cell biology↗

bioRxiv2019

Dietary restriction induces post-transcriptional regulation of longevity genes.

Dietary restriction increases lifespan through adaptive changes in gene expression. To understand more about these changes, we analyzed the transcriptome and translatome of C. elegans subjected to dietary restriction. Transcription of muscle regulatory and structural genes increased, while increased expression of amino acid metabolism and neuropeptide signaling genes was controlled at the level of translation. Evaluation of post-transcriptional regulation identified putative roles for RNA binding proteins, RNA editing, microRNA, alternative splicing, and nonsense mediated decay in response to nutrient limitation. Using RNA interference, we discovered several differentially expressed genes that regulate lifespan. We also found a compensatory role for translational regulation, which offsets dampened expression of a large subset of transcriptionally downregulated genes. Furthermore, 3 UTR editing and intron retention increase under dietary restriction and correlate with diminished translation, while trans-spliced genes are refractory to reduced translation efficiency compared to messages with the native 5 UTR. Finally, we find that smg-6 and smg-7, which are genes governing selection and turnover of nonsense mediated decay targets, are required for increased lifespan under dietary restriction.

genomics↗