Biology subjects

Beuret, N.

Publications and source records attributed to Beuret, N..

4 recordsLinked to original sources

bioRxiv2026

A combinatorial pre-mRNP retention factor network couples nuclear speckle architecture to splicing quality control

Cells must prevent incompletely spliced transcripts from entering the cytoplasm, yet how splicing status is recognized and converted into selective nuclear retention remains unclear. Here, we identify a network of RNA-binding proteins that retain pre-mRNPs within nuclear speckles. Proteomic analysis of splicing intermediates accumulated in nuclear speckles identified a set of retention factors including BCLAF1, THRAP3 and SRSF7 that anchor pre-mRNPs to the SON scaffold and are required for pre-mRNP retention in speckles. Distinct RNA-binding patterns and transcript-specific retention factor requirements suggest that multiple mRNP features tune retention combinatorially. Super-resolution imaging revealed that the SON and SRRM2 speckle scaffolds form interdigitated networks with RNA enriched along networks and within interstitial speckle lumens. This architecture remodels in response to pre-mRNP load and is disrupted upon depletion of retention factors. Together, these findings define a pre-mRNP quality-control pathway that links splicing state to nuclear retention and the dynamic organization of nuclear speckles.

cell 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↗

bioRxiv2024

Tag with Caution - How protein tagging influences the formation of condensates

Fluorescent proteins and peptide tags are essential tools in cellular biology, but can alter the biochemical properties of target proteins. Biomolecular condensates, which have emerged as key principles of cellular organization, are suggested to provide robustness to cells, yet they can also respond sensitively to small changes in environmental conditions--or tagging of their components, as our findings suggest. Here, we investigated the effects of sixteen widely used tags on condensate formation in various model organisms, in vitro, in cells and by computational modelling. We find that tagging strongly influenced condensation for some proteins, while others remained unaffected. Effects varied, with some tags enhancing and others decreasing condensation, and depended on the protein being tagged. Coarse-grained simulations suggest that the charge of the fluorescent protein tags is a critical factor modulating condensation behavior. Together, our results underscore the importance of rigorous experimental design and interpretation in condensate experiments.

molecular biology↗

bioRxiv2021

Small disulfide loops in peptide hormones mediate self-aggregation and secretory granule sorting

Unlike constitutively secreted proteins, peptide hormones are stored in densely packed secretory granules, before regulated release upon stimulation. Secretory granules are formed at the trans-Golgi network (TGN) by self-aggregation of prohormones as functional amyloids. The nonapeptide hormone vasopressin, which forms a small disulfide loop, was shown to be responsible for granule formation of its precursor in the TGN as well as for toxic fibrillar aggregation of unfolded mutants in the endoplasmic reticulum (ER). Several other hormone precursors also contain similar small disulfide loops suggesting their function as a general device to mediate aggregation for granule biogenesis. To test this hypothesis, we studied the capacity of small disulfide loops of different hormone precursors to mediate aggregation in the ER and the TGN. They indeed induced ER aggregation although to different extents in Neuro-2a and COS-1 cells. Fused to a constitutively secreted reporter protein, they also promoted sorting into secretory granules, enhanced stimulated secretion, and increased Lubrol insolubility in AtT20 cells. These results support the hypothesis that small disulfide loops act as novel signals for secretory granule biogenesis and sorting by self-aggregation.

cell biology↗