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Biology subjects

Hermon, A. S.

Publications and source records attributed to Hermon, A. S..

2 recordsLinked to original sources

Essential role for Nup43 in Drosophila fertility and spermiogenesis through Myosin VI-dependent actin cone assembly dynamics

Nuclear pore complexes, composed of nucleoporins (Nups), are critical for bidirectional nucleocytoplasmic transport. Studies on Nups have linked them with various cellular processes, including cell division, contributing significantly to organismal development. Intriguingly, Nup43, an integral member of Nup107 complex, is linked with premature ovarian insufficiency in humans. Here, we report that Nup43 is integral to the maintenance of Drosophila fertility. Both the females and males of Nup43 null mutant are sterile. In Nup43 mutants, embryonic development is halted at the first division stage, and males are sterile due to an arrest at the canoe stage of spermiogenesis. The nuclear elongation, shaping, and actin cone assembly steps of individualization complex formation are adversely affected, suspending sperm maturation. Expression through Nup43 transgene in Nup43 null mutants completely rescues spermiogenesis defects. Actin-based motor, Myosin VI (jar), interacts with Nup43 and rescues the actin cone assembly but not the sterility defects. We have uncovered a novel non-canonical function for Nup43 in Drosophila spermiogenesis, and propose that Nup43, along with jar, facilitates sperm individualization by promoting actin cone assembly.

developmental biology↗

Synergistic DNA and RNA binding of the Hox transcription factor Ultrabithorax coordinates splicing and shapes in vivo homeotic functions

The dual interaction of many transcription factors (TFs) with both DNA and RNA is an underexplored issue that could fundamentally reshape our understanding of gene regulation. We address this central issue by investigating the RNA binding activity of the Drosophila Hox TF Ultrabithorax (Ubx) in alternative splicing and morphogenesis. Relying on molecular and genetic interactions, we uncover a homodimerization-dependent mechanism by which Ubx regulates splicing. Notably, this mechanism enables the decoupling of Ubx-DNA and -RNA binding activity in splicing. We identify a critical residue for Ubx-RNA binding and demonstrate the essential role of Ubx-RNA binding ability for its homeotic functions. Overall, we uncover a unique mechanism for Ubx-mediated splicing and underscore the critical contribution of synergistic DNA/RNA binding for its morphogenetic functions. These findings advance our understanding of co-transcriptional regulation and highlight the significance of TF-DNA/RNA synergistic function in shaping gene regulatory networks in living organisms. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/612310v1_ufig1.gif" ALT="Figure 1"> View larger version (65K): org.highwire.dtl.DTLVardef@6b3f84org.highwire.dtl.DTLVardef@116f353org.highwire.dtl.DTLVardef@1c0ceb4org.highwire.dtl.DTLVardef@142906c_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIUbx homodimerization enables decoupling of DNA- and RNA-dependent splicing regulation C_LIO_LIThe homeodomain K58 amino acid is critical for Ubx-RNA binding ability C_LIO_LIUbx-RNA binding ability is essential for splicing regulation C_LIO_LIDual DNA/RNA binding activities shape Ubx homeotic functions C_LI

molecular biology↗