Biology subjects

Engström, Y.

Publications and source records attributed to Engström, Y..

3 recordsLinked to original sources

bioRxiv2025

A Non-Transcriptional Mitotic Function of POU/Oct Factors Ensures Spindle Stability and Chromosome Segregation

POU/Oct transcription factors are critical regulators of cellular processes, including proliferation, cell fate determination, and cancer. Despite their importance, the specific molecular mechanisms by which they influence cell division remain largely unclear. Here, we show that Nub/Pdm1, a Drosophila homolog of human POU2F1/Oct1, is essential for accurate mitotic progression in a non-transcriptional manner. Live imaging and immunostaining in Drosophila embryos reveal that its depletion leads to disorganized spindles, aberrant chromosome segregation and delayed mitotic progression. Similarly, reduction of POU2F1/Oct1 in live human cells caused disorganized mitotic spindles and spindle collapse. Nub/Pdm1 is enriched within the mitotic spindles and this recruitment is independent of its sequence-specific DNA binding. Instead, it depends on the integrity of spindle microtubules and is regulated by mitosis-related motor proteins, and kinases. Our findings identify both fly Nub/Pdm1 and human Oct1 as important regulators of mitotic progression, acting to maintain spindle stability and proper elongation. The non-transcriptional mitotic role of Nub/Pdm1 reveals a previously unrecognized mechanism of POU/Oct proteins and provides new insight into their potential oncogenic properties. Highlights- Nub/Pdm1 is vital for accurate mitotic progression in a non-transcriptional manner - Nub/Pdm1 preserves spindle integrity during rapid syncytial nuclear divisions - Nub/Pdm1 spindle enrichment depends on mitotic factors and intact microtubules - Nub and human Oct1 ensure proper chromosome segregation

cell biology↗

bioRxiv2025

The mRNA architecture of the termination site primes programmed stop codon readthrough events in Drosophila

Programmed stop codon readthrough (SCR) is a form of genetic re-coding, in which a near-cognate tRNA base-pairs with a stop codon, leading to the translation of a C-terminally extended protein. Recent studies revealed that SCR represents an evolutionarily conserved, spatio-temporally controlled mechanism of posttranscriptional gene regulation that requires cis-regulatory elements as well as trans-acting factors. In this study, we characterized cis-regulatory elements controlling programmed SCR of the Drosophila POU3-family member drifter/ventral veins lacking (dfr/vvl). Using S2 cell-based luciferase assays, we show that stop codon identity and the +4 to +9 nucleotide sequence are required but not sufficient for dfr SCR regulation. Phylogenetic prediction identified an mRNA stem-loop in the 3 UTR, proximal to the readthrough UAG codon. Mutational analysis revealed that the distance from the stop codon as well as stem-loop stability, but not the underlying sequence identity, critically impact dfr SCR. Similarly, the mRNA stem-loop promoted SCR in an in vivo Drosophila model. We applied this information to refine computational prediction of SCR-associated mRNA stem-loops and show that these elements effectively promote SCR of heterologous mRNAs. These findings increase our understanding of SCR and the underlying regulatory mechanisms. Key PointsO_LIStop codon readthrough is regulated both by mRNA sequence identity and mRNA structure elements. C_LIO_LIA 3 mRNA stem-loop and its thermodynamic stability determine stop codon readthrough efficiency. C_LIO_LImRNA stem-loops are frequently found in Drosophila genes that exhibit stop codon readthrough. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=174 SRC="FIGDIR/small/685291v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@dbccf6org.highwire.dtl.DTLVardef@6d53f3org.highwire.dtl.DTLVardef@1a27deborg.highwire.dtl.DTLVardef@f8e5ae_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2020

Bab2 activates JNK signaling to reprogram Drosophila wing disc development

In response to cellular stress and damage, certain tissues are able to regenerate and to restore tissue homeostasis. In Drosophila imaginal wing discs, dying cells express mitogens that induce compensatory proliferation in the surrounding tissue. Here we report that high levels of the BTB/POZ transcription factor Bab2 in the posterior compartment of wing discs activates c-Jun N-terminal kinase (JNK) signaling and local, cell-autonomous apoptotic cell death. This in turn triggered the upregulation of the Dpp mitogen and cellular proliferation in the anterior compartment in a JNK-dependent manner. In the posterior compartment, however, dpp expression was suppressed, most likely by direct transcriptional repression by Bab2. This dual-mode of JNK-signaling, autocrine pro-apoptotic signaling and paracrine pro-proliferative signaling, led to opposite effects in the two compartments and reprogramming of the adult wing structure. We establish Bab2 as a regulator of wing disc development, with the capacity to reprogram development via JNK activation in a cell-autonomous and non-cell-autonomous manner. Summary statementZhao et al. shows that the BTB/POZ transcription factor Bab2 is a potent activator of JNK signaling, apoptosis and compensatory proliferation, thereby driving both pro-tumorigenic and anti-tumorigenic processes.

developmental biology↗