Biology subjects

Nelson, J. O.

Publications and source records attributed to Nelson, J. O..

4 recordsLinked to original sources

bioRxiv2024

Insulin signaling regulates R2 retrotransposon expression to orchestrate transgenerational rDNA copy number maintenance

Preserving a large number of essential yet highly unstable ribosomal DNA (rDNA) repeats is critical for the germline to perpetuate the genome through generations. Spontaneous rDNA loss must be countered by rDNA copy number (CN) expansion. Germline rDNA CN expansion is best understood in Drosophila melanogaster, which relies on unequal sister chromatid exchange (USCE) initiated by DNA breaks at rDNA. The rDNA-specific retrotransposon R2 responsible for USCE-inducing DNA breaks is typically expressed only when rDNA CN is low to minimize the danger of DNA breaks; however, the underlying mechanism of R2 regulation remains unclear. Here we identify the insulin receptor (InR) as a major repressor of R2 expression, limiting unnecessary R2 activity. Through single-cell RNA sequencing we find that male germline stem cells (GSCs), the major cell type that undergoes rDNA CN expansion, have reduced InR expression when rDNA CN is low. Reduced InR activity in turn leads to R2 expression and CN expansion. We further find that dietary manipulation alters R2 expression and rDNA CN expansion activity. This work reveals that the insulin pathway integrates rDNA CN surveying with environmental sensing, revealing a potential mechanism by which diet exerts heritable changes to genomic content.

cell biology↗

bioRxiv2021

The retrotransposon R2 maintains Drosophila ribosomal DNA repeats

Ribosomal DNA (rDNA) loci contain the hundreds of tandemly repeated copies of ribosomal RNA genes needed to support cellular viability. This repetitiveness makes it highly susceptible to copy number (CN) loss, threatening multi-generational maintenance of rDNA. How this threat is counteracted to avoid extinction of the lineage has remained unclear. Here, we show that the rDNA-specific retrotransposon R2 is essential for rDNA CN maintenance in the Drosophila male germline, despite the perceived disruptive nature of transposable elements. Depletion of R2 led to defective rDNA CN maintenance, causing a decline in fecundity over generations and eventual extinction. This study reveals that active retrotransposons can provide a benefit to their hosts, contrary to their reputation as genomic parasites, which may contribute to their widespread success throughout taxa. One Sentence SummaryThe retrotransposon R2 initiates restoration of ribosomal DNA copies to trans-generationally maintain essential locus.

cell biology↗

bioRxiv2017

Smg5 is required for multiple nonsense-mediated mRNA decay pathways in Drosophila

The nonsense-mediated mRNA decay (NMD) pathway is a cellular quality control and post-transcriptional gene regulatory mechanism and is essential for viability in most multicellular organisms. A complex of proteins has been identified to be required for NMD function to occur, however the individual contribution of each of these factors to the NMD process is not well understood. Central to the NMD process are two proteins Upf1 (SMG-2) and Upf2 (SMG-3), which are found in all eukaryotes and are absolutely required for NMD in all organisms in which it has been examined. The other known NMD factors, Smg1, Smg5, Smg6, and Smg7 are more variable in their presence in different orders of organisms, and are thought to have a more regulatory role. Here we present the first genetic analysis of the NMD factor Smg5 in Drosophila. Surprisingly, we find that unlike the other analyzed Smg genes in this organism, Smg5 is essential for NMD activity. We found this is due at least in part to a role for Smg5 in the activity of two separable NMD-target decay mechanisms: endonucleolytic cleavage and 5'-to-3' exonucleolytic decay. Redundancy between these degradation pathways explains why some Drosophila NMD genes are not required for all NMD-pathway activity. We also found that while the NMD component Smg1 has only a minimal role in Drosophila NMD during normal conditions, it becomes essential when NMD activity is compromised by partial loss of Smg5 function. Our findings suggest that not all NMD complex components are required for NMD function at all times, but instead are utilized in a context dependent manner in vivo.

genetics↗

bioRxiv2017

Transgenerational dynamics of rDNA copy number in Drosophila male germline stem cells

rDNA loci, composed of hundreds of tandemly duplicated arrays of rRNA genes, are known to be among the most unstable genetic elements due to their repetitive nature. rDNA instability underlies aging (replicative senescence) in yeast cells, however, its contribution to the aging of multicellular organisms is poorly understood. In this study, we investigate the dynamics of rDNA loci during aging in the Drosophila male germline stem cell (GSC) lineage, and show that rDNA copy number decreases during aging. Our study further reveals that this age-dependent decrease in rDNA copy number is heritable from generation to generation, yet GSCs in animals that inherit reduced rDNA copy number are capable of recovering normal rDNA copy number. Based on these findings, we propose that rDNA loci are dynamic genetic elements, where rDNA copy number changes dynamically yet is maintained through a recovery mechanism in the germline.

developmental biology↗