Biology subjects

Keller Valsecchi, C. I.

Publications and source records attributed to Keller Valsecchi, C. I..

6 recordsLinked to original sources

bioRxiv2026

Persistent maternal memory, transient offspring effects: the temporal and sex-specific architecture of heritable heat-stress responses in zebrafish

Environmental experiences can influence subsequent generations, yet little is known about the dynamics of such molecular memories across time, reproduction events, and offspring development. Here we provide a temporal map of the transmission of environmental information through egg provisioning and its phenotypic consequences in zebrafish. Specifically, we follow the effects of a 2-week heat wave across successive matings and two unexposed generations along a complete adult-to-egg-to-adult experimental trajectory, assessing gonad responses, maternal RNA, embryo survival, larval behaviour, adult stress resistance and liver transcriptomes. We find that oocyte maternal RNA retained a pronounced heat-shock signature across several weeks and multiple spawning events, with selected functional components persisting into oocytes of the next generation. Somatic responses followed a fundamentally different trajectory: effects on liver transcription were sex- and timepoint-specific, with minor intergenerational signatures of energy metabolism and metabolic stress in males. Parental heat exposure also altered offspring survival, larval behaviour and thermal tolerance, with progressively weakened effects across successive reproductive events and across generations. Our results reveal distinct temporal dynamics of environmental memory in the germline vs the developing and adult soma, with persistent molecular information in maternal provisioning coexisting with progressively fading offspring phenotypes. Such selective retention and loss of parental information align with theoretical predictions about the progressively declining value of inherited information and may determine the dynamics of cross-generational population-level responses to extreme events.

evolutionary biology↗

bioRxiv2026

PAIP1 couples mRNA export to cytoplasmic mRNP remodeling and poly(A) homeostasis

Messenger ribonucleoproteins (mRNPs) acquire distinct protein compositions as they move from the nucleus to the cytoplasm, yet how this transition is coordinated and how inefficient remodeling affects downstream mRNA metabolism remains poorly understood. Here, we identify PAIP1 as a metazoan cofactor of the mRNA export ATPase DDX19. By binding a conserved N-terminal motif in DDX19, PAIP1 is recruited to the nuclear pore, where it promotes exchange of the nuclear poly(A)-binding protein PABPN1 for cytoplasmic PABPC1, thereby coupling mRNA export to cytoplasmic mRNP maturation. PAIP1 depletion alters cytoplasmic mRNP composition, mRNA stability and poly(A)-tail homeostasis. In Drosophila embryos, where poly(A)-tail regulation of maternal mRNAs directs early development, maternal PAIP1 depletion shortens poly(A)-tails, delays zygotic genome activation, and causes severe developmental defects. Our findings identify an export-coupled mRNP maturation pathway linking PABP exchange to downstream mRNA metabolism.

molecular biology↗

bioRxiv2026

The splicing paralogues SNRPB and SNRPN control differential metabolic states.

Gene duplication underlies evolutionary innovation, yet many paralogues remain highly similar, raising questions about their functional divergence and physiological relevance. The spliceosomal Sm core protein SNRPB and its mammalian-specific paralogue SNRPN share over 90% sequence identity, but their distinct expression patterns - SNRPB being ubiquitous and SNRPN confined to the brain - suggest specialized functions. Why mammals have two different spliceosomes has remained obscure. Here, we generated isogenic human cell lines expressing ectopically either SNRPB or SNRPN exclusively and found that SNRPN stabilizes transcripts involved in energy metabolism and mitochondrial function, leading to increased mitochondrial abundance and oxygen consumption. Despite similar spliceosomal interactomes, SNRPN more strongly associates with the PRMT5 methylosome complex and exhibits dynamic arginine methylation in its C-terminal region that is sensitive to translation inhibition and amino acid availability. The SNRPN-dependent transcriptome responds to translation inhibition by stabilizing long, intron-rich genes involved in amino acid and energy metabolism. Our findings reveal a nutrient-sensitive, methylation-dependent mechanism that differentiates the two paralogues. This suggests that SNRPN functions as a metabolic-specialized spliceosomal subunit thereby providing tissue-specific adaptation of RNA processing in mammals.

molecular biology↗

bioRxiv2025

Convergent Evolution of H4K16ac-mediated Dosage Compensation Shapes Sex-dependent Lifespan in a ZW Species

Sex chromosomes impact chromatin organization and histone modification dynamics differently between males and females, particularly those involved in dosage compensation (DC). The stability of DC mechanisms may shape sex-specific phenotypes and traits such as lifespan. However, the tissue- and age-dependent variations as well as the evolutionary diversity of DC mechanisms are incompletely understood. Here, we investigate the occurrence of histone H4 lysine 16 acetylation (H4K16ac), previously known for its role in sex chromosome DC in the male-heterogametic fruit fly Drosophila melanogaster and the green anole lizard Anolis carolinensis. By sampling multiple arthropods, we find the convergent evolution of H4K16ac for DC in a female-heterogametic (ZW) species, the crustacean Artemia franciscana. CUT&Tag analysis demonstrates that H4K16ac is confined to the non-recombining stratum of the Z chromosome in females. H4K16ac-mediated DC is established during embryogenesis, sustained until adulthood, but then becomes reconfigured and variable in aged females. Interfering with acetylation alleviates male-female differences in lifespan. Our findings shed light on the evolutionary diversity of DC across species. They highlight histone acetylation as a sex-specific vulnerability linked to the chromatin landscape of sex chromosomes and its potential role in driving male-female differences.

evolutionary biology↗

bioRxiv2024

Sex-specific transcriptome dynamics of Anopheles gambiae during embryonic development

Malaria-transmitting mosquitoes are extremely sexually dimorphic in their anatomy and behaviour. Sex-specific gene expression in Anopheles gambiae is well-studied in adult stages, but its onset during embryogenesis, apart from sex-determination factors like Yob, remains largely unknown. Here, we report a comprehensive single-embryo transcriptome atlas of A. gambiae males and females to understand the earliest stages of establishing the sex-specific expression networks. Our dataset reveals embryonic RNA isoform diversity including a global shift towards distal alternative polyadenylation (APA) sites during the maternal-to-zygotic genome transition. Sex-biased gene expression and alternative splicing are limited during embryogenesis, with most sex-specific patterns emerging post- embryonically. X chromosome dosage compensation is established shortly after zygotic genome activation concomitant with direct binding of the master regulator protein SOA to X- linked promoters. Unlike the dosage compensation regulators in Drosophila or mammals, SOA operates in a one-step fashion, directly binding CA-rich promoter motifs without prioritizing certain gene groups over others. We propose that the Anopheles dosage compensation system represents an evolutionary endpoint of a gene-by-gene regulatory mechanism that evolved to a chromosome-wide scale.

molecular biology↗

bioRxiv2023

Systematic discovery of protein interaction interfaces using AlphaFold and experimental validation

Structural resolution of protein interactions enables mechanistic and functional studies as well as interpretation of disease variants. However, structural data is still missing for most protein interactions because we lack computational and experimental tools at scale. We thoroughly assessed AlphaFold-Multimer accuracy for structure prediction of interactions involving folded domains binding to short linear motifs from the ELM database. The structure predictions were highly sensitive but not very specific when using small protein fragments. Sensitivity decreased substantially when using long protein fragments or full length proteins with intrinsically disordered regions. We delineated a fragmentation strategy to optimize sensitivity and applied it to interactions between proteins associated with neurodevelopmental disorders. This enabled prediction of highly confident and likely disease-related novel interfaces, but also resulted in many high scoring false positive predictions. Experiments supported predicted interfaces between CREBZF-HCFC1, FBXO23-STX1B, STX1B-VAMP2, ESRRG-PSMC5, PEX3-PEX19, PEX3-PEX16, and SNRPB-GIGYF1 providing novel molecular insights for diverse biological processes. Our work highlights exciting perspectives, but also reveals clear limitations and the need for future developments to maximize the power of Alphafold-Multimer for interface predictions.

systems biology↗