TDP-43 regulates mitochondrial dsRNA accumulation and chromosome territory formation during prophase I of Drosophila male meiosis
Year: 2026
Type: article
Abstract: TDP-43 is a conserved RNA/DNA-binding protein infamous for its pathological roles in numerous human neurodegenerative diseases. However, TDP-43 is expressed in diverse cell types and its evolved biological functions are unclear. We show that Drosophila TDP-43 homolog (TBPH) and its retrocopy (Cocoon) are expressed in prophase I of male meiosis and promote regulated expression of abundant double-stranded RNAs (dsRNAs) in spermatocyte nuclei. dsRNAs progressively fill the nucleoplasm during chromosome territory (CT) formation, a noncanonical meiotic process in Drosophila males where unidentified dispersive forces segregate chromosomes into distinct domains and disrupt heterologous pairing events that could cause nondisjunction. tbph deficiency causes premature dsRNA accumulation and pairing defects, which are rescued by human TDP-43 expression. Conversely, spermatocytes lacking cocoon show reduced dsRNA, defective chromosome territory formation and heterologous chromosome contacts. Nuclear dsRNAs colocalize with Blanks, a dsRNA-binding protein required for male fertility. Surprisingly, dsRIP sequencing reveals that dsRNAs are mitochondrial in origin.
Source: Communications Biology
Institutions: Brown University, Rhode Island College
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,190
Awards: Predoctoral Training Program in Biological Data Science at Brown University, G2559423996, The effect of life span modifying interventions on Alzheimer's Disease in Drosophila and Mice., G9000095838, Bloomington Drosophila Stock Center at Indiana University, Role of Retrotransposon Activity in Neurodegeneration and Alzheimer's Disease
OpenAlex ID: W7220845350