Biology subjects

Panse, V. G.

Publications and source records attributed to Panse, V. G..

6 recordsLinked to original sources

bioRxiv2026

A nucleolar assembly module integrates an ancestral isoaspartylase to safeguard ribosome biogenesis

Eukaryotes inherited the core ribosome biogenesis apparatus from archaea. However, nucleocytoplasmic compartmentalisation and expansion to >200 assembly factors created the challenge of integrating this ancestral machinery into a complex maturation programme. One solution is the formation of transient modules in which newly acquired assembly factors support deeply conserved components. Here, we identify such a module, centred on the ancestral isoaspartylase Fap7, which couples the modification of the ribosomal protein uS11 to its incorporation into pre-ribosomes. Fap7 partners with Krr1 to capture uS11, forming an early checkpoint in which uS11 loading licenses Kri1 engagement and assembly progression. Loss of uS11 modification triggers a late checkpoint, preventing aberrant pre-ribosomes from acquiring translational competence. Integrative structure-function studies reveal how the ancestral isoaspartylase is embedded within a conserved eukaryotic assembly-factor network to safeguard the timing, order, and fidelity of ribosome production.

biochemistry↗

bioRxiv2025

An inositol pyrophosphate interaction screen provides insight into the regulation of plant casein kinase II

Inositol pyrophosphates (PP-InsPs) are key nutrient messengers in plants, but their protein receptors remain poorly defined. Using a systems-level affinity screen with biotinylated InsP, InsP, and InsP in Arabidopsis thaliana, we identify multiple conserved PP-InsP-interacting complexes involved in mRNA metabolism, translation, and cell signaling, including the nuclear -subunits of casein kinase II (CK2). The CK2 subunit AtCKA1 associates with the PP-InsP kinase AtVIH2, and its 1.9 [A] crystal structure with InsP6 reveals two conserved PP-InsP binding sites located in the N-and C-terminal lobes. AtCKA1 binds InsP6, InsP7, and InsP8 with micromolar affinity. Mutation of both binding sites in the AtCKA6xmut mutant abolishes PP-InsP binding in vitro. AtCKA6xmut partially rescues the flowering phenotype of ck2a1/2/3 mutants, and equivalent mutations inactivate the yeast orthologs ScCka1 and ScCka2. InsP6 competitively inhibits phosphorylation of canonical CK2 substrates by occupying a basic substrate-binding groove. Although incorporating {beta}-subunits strongly enhances the phosphorylation of substrates by the AtCK2 holoenzyme, ck2b1/2/3/4 mutants exhibit only mild growth defects in Arabidopsis. In Marchantia, loss of the single ck2a gene severely impairs growth, whereas deletion of the {beta} subunit has no effect. Together, our findings suggest that InsP6/PP-InsPs modulate the activity of the isolated CK2 -subunit by regulating access to its substrate-binding site.

plant biology↗

bioRxiv2025

The Legionella effector RidL promotes mitochondrial fragmentation through phosphorylation activation of the large GTPase Drp1

Intracellular pathogens such as Legionella pneumophila secrete effector proteins that manipulate host cell processes to promote bacterial survival. One such effector, RidL, is known to inhibit retrograde trafficking by interacting with the retromer complex via its N-terminal domain. Here, we identify a second function of RidL mediated by its C-terminal domain, which directly binds to the mitochondrial fission GTPase Drp1 and related large GTPases. In vitro, RidL reduces Drp1 GTPase activity and disrupts its oligomerization. During infection, RidL localizes to mitochondria, enhances the accumulation of Drp1 and the outer membrane protein Tom20, and impairs mitochondrial dynamics and function. Moreover, in L. pneumophila-infected cells, RidL promotes phosphorylation of Drp1 at Ser616, leading to Drp1 activation and mitochondrial fragmentation. These findings establish RidL as a bifunctional effector that targets both the retromer complex and Drp1 through distinct domains. By interfering with host mitochondrial dynamics, RidL enables L. pneumophila to remodel host organelles and optimize conditions for intracellular replication.

microbiology↗

bioRxiv2024

Stm1 regulates Ifh1 activity revealing crosstalk between ribosome biogenesis and ribosome dormancy

Ribosome abundance in changing environments is governed by biogenesis and degradation, but the underlying mechanisms regulating these opposing processes remain unknown. Here we show that Suppressor of Tom1 (Stm1), a dormancy factor protecting cytosolic ribosomes during starvation, has an unexpected function to promote ribosome biogenesis during exponential growth conditions. Indeed, Stm1 transiently localizes to the nucleolus and engages with pre-ribosomal particles. Stm1 upregulates transcription of ribosomal protein genes by directly binding the activation domain (AD) of the transcription factor Ifh1. These novel Stm1 functions confer rapamycin-sensitivity and are mediated by its C-terminal intrinsically disordered region (IDR), which is dispensable for ribosome hibernation. We conclude that Stm1 regulates ribosome homeostasis linking ribosome biogenesis and ribosome dormancy.

cell biology↗

bioRxiv2022

The structure of yeast Npl3 bound to RNA reveals a cooperative sequence-specific recognition and an RNA chaperone role in splicing

The conserved SR-like protein Npl3 promotes splicing of diverse pre-mRNAs. However, the RNA sequence(s) recognized by the RNA Recognition Motifs (RRM1 & RRM2) of Npl3 during the splicing reaction remain elusive. Here, we developed a split-iCRAC approach in yeast to uncover the consensus sequence bound to each RRM. High-resolution NMR structures show that RRM2 recognizes a 5-GNGG-3 motif leading to an unusual mille-feuille topology. These structures also reveal how RRM1 preferentially interacts with a CC-dinucleotide upstream of this motif, and how the inter-RRM linker and the region C-terminal to RRM2 contributes to cooperative RNA-binding. Structure-guided functional studies show that Npl3 genetically interacts with U2 snRNP specific factors and we provide evidence that Npl3 melts U2 snRNA stem-loop I, a prerequisite for U2/U6 duplex formation within the catalytic center of the Bact spliceosomal complex. Thus, our findings provide insights into an unanticipated RNA chaperoning role for Npl3 during spliceosome active site formation.

biophysics↗

bioRxiv2018

Conserved phosphorylation hotspots in eukaryotic protein domain families

Protein phosphorylation is the best characterized post-translational modification that regulates almost all cellular processes through diverse mechanisms such as changing protein conformations, interactions, and localization. While the inventory for phosphorylation sites across different species has rapidly expanded, their functional role remains poorly investigated. Here, we have combined 537,321 phosphosites from 40 eukaryotic species to identify highly conserved phosphorylation \"hotspot\" regions within domain families. Mapping these regions onto structural data revealed that they are often found at interfaces, near catalytic residues and tend to harbor functionally important phosphosites. Notably, functional studies of a phospho-deficient mutant in the C-terminal hotspot region within the Ribosomal S11 domain in the yeast ribosomal protein uS11 showed cold-sensitive phenotype and impaired 20S pre-rRNA processing. Altogether, our study identified phosphorylation hotspots for 162 protein domains suggestive of an ancient role for the control of diverse eukaryotic domain families.

cell biology↗