bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2024.03.28.587005

Extended longevity of termite kings and queens is accompanied by extranuclear localization of telomerase in somatic organs and caste-specific expression of its isoforms

Pangracova, M.·Krivanek, J.·Vrchotova, M.·Sehadova, H.·Hadravova, R.·Hanus, R.·Luksan, O.
View original source ↗Export metadata ↓

Abstract

Kings and queens of termites are endowed with an extraordinary longevity coupled with lifelong fecundity. We recently reported that termite kings and queens display a dramatically increased enzymatic activity and abundance of telomerase in their somatic organs when compared to short-lived workers and soldiers. We hypothesized that this telomerase activation may represent a non-canonical pro-longevity function, independent of its canonical role in telomere maintenance. Here, we explore this avenue and investigate whether the presumed non-canonical role of telomerase may be due to alternative splicing of the catalytic telomerase subunit TERT and whether the subcellular localization of TERT isoforms differs among organs and castes in the termite Prorhinotermes simplex. We empirically confirm the expression of four in silico predicted splice variants (psTERT1-A, psTERT1-B, psTERT2-A, psTERT2-B), defined by N-terminal splicing implicating differential localizations, and C-terminal splicing giving rise to full-length and truncated isoforms. We show that the transcript proportions of the psTERT are caste- and tissue-specific and that the extranuclear full-length isoform TERT1-A is relatively enriched in the soma of neotenic kings and queens compared to their gonads and to the soma of workers. We also show that extranuclear TERT protein quantities are significantly higher in the soma of kings and queens compared to workers, namely due to the cytosolic TERT. Independently, we confirm by microscopy the extranuclear TERT localization in somatic organs. We conclude that the presumed pleiotropic action of telomerase combining the canonical nuclear role in telomere maintenance with extranuclear functions is driven by complex TERT splicing.

Source connections

Explore related subjects

molecular biologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Pangracova, M., Krivanek, J., Vrchotova, M., Sehadova, H., Hadravova, R., Hanus, R., Luksan, O.. 2024-03-29. Extended longevity of termite kings and queens is accompanied by extranuclear localization of telomerase in somatic organs and caste-specific expression of its isoforms. https://doi.org/10.1101/2024.03.28.587005

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

An ssRNA Phage Single-gene Lysis Protein Targeting MraY Reveals Convergent Evolution Across the RNA-DNA Phage Boundary

Small lytic phages of the ssRNA Leviviricetes and ssDNA Microviricetes achieve host lysis by expression of a single protein, designated as an Sgl protein. Four ssRNA Sgls have been shown to inhibit steps in peptidoglycan biosynthesis: three target MurJ, the Lipid II flippase, and one targets MurA, the committed step of the pathway. A fifth Sgl, the E protein of the canonical ssDNA microvirus {varphi}X174, inhibits MraY, which catalyzes the synthesis of the first lipid-linked intermediate. This inhibition requires SlyD, a cytoplasmic FKBP-type peptidyl-prolyl cis-trans isomerase. The Sgl of the Caulobacter ssRNA phage {varphi}Cb5 (Cebevirus halophobicum) has not been characterized. Here, we present physiological evidence that Sgl{varphi}Cb5 targets MraY. Moreover, we show that, despite the absence of detectable sequence similarity, Sgl{varphi}Cb5 shares several features with the {varphi}X174 E protein, including the distribution of hydrophobic and charged residues, a proposed N-out, C-in membrane topology, and retention of lytic activity in an Sgl{varphi}Cb5 -LacZ fusion. Furthermore, expression of the Caulobacter cytoplasmic FKBP-type peptidyl-prolyl cis-trans isomerase CC2799 enhances Sgl{varphi}Cb5 -mediated lysis in E. coli. These parallels between Sgl function in a DNA phage and an RNA phage either represent remarkably consonant convergent evolution or some evolutionary cross-over event for which there is currently no precedent.

molecular biology↗
bioRxiv2026

HERC1-mediated orphan subunit quality control maintains proteasome homeostasis and is disrupted in HERC1-associated neurodevelopmental disease

Biallelic hypomorphic variants in the E3 ubiquitin ligase HERC1 cause a neurological disorder clinically characterized by macrocephaly, dysmorphic facies, and psychomotor delay. Identifying the substrates of HERC1 is essential for understanding its biological functions and the mechanisms underlying disease-associated variants. To address this, we performed a quantitative proteomic analysis using biotinylated ubiquitin to identify HERC1 targets and examine their regulation in cells expressing HERC1 with or without ubiquitin ligase activity. This approach revealed a broad set of HERC1-dependent ubiquitylation substrates, including proteins from major multiprotein complexes such as the proteasome, the translation initiation machinery, and pathways involved in cell metabolism. Focusing on the proteasome, the most prominently represented complex, we identified several regulatory particle subunits, including PSMC6, PSME1, and PSME2. Specifically, within the 19S regulatory particle, we demonstrated that ubiquitylation of the PSMC6 subunit involves the formation of K48-linked polyubiquitin chains and depends on HERC1 activity. Other 19S subunits, such as PSMC2, PSMC4, and PSMC5, undergo a similar modification. Mechanistically, we show that HERC1 selectively recognizes unassembled subunits, promotes their ubiquitylation, and targets them for proteasomal degradation. Notably, in HERC1-deficient cells, disruption of this mechanism impaired proteasomal activity. At the disease level, quantitative proteomic analysis of the pathogenic HERC1 variant c.1448G>A (p.Gly483Glu) likewise identified altered ubiquitylation of proteasome subunits and components of the translation initiation machinery. Biochemical analyses further revealed impaired ubiquitylation of PSMC6 by the mutant HERC1 protein, associated with a loss of interaction between HERC1 and PSMC6. Together, these findings establish a link between HERC1-associated neurological disorders and defective ubiquitylation pathways. They elucidate the molecular mechanisms by which HERC1 regulates proteostasis and demonstrate how disruption of these processes contributes to disease pathogenesis, thereby highlighting potential avenues for therapeutic intervention.

molecular biology↗
bioRxiv2026

PKR inhibition prevents maladaptive responses to endoplasmic reticulum (ER) stress in early-onset dystonia DYT-PRKRA.

DYT-PRKRA is a rare, childhood-onset dystonia caused by mutations in the PRKRA gene, which encodes the protein PACT. PACT activates protein kinase R (PKR) in response to endoplasmic reticulum (ER) stress. In DYT-PRKRA patient cells, the PACT-PKR interaction is enhanced, increasing sensitivity to ER stress-induced apoptosis. The canonical protein kinase activated by ER stress is PKR-like endoplasmic reticulum kinase (PERK), which phosphorylates the subunit of eukaryotic translation initiation factor 2 (eIF2) to initiate the integrated stress response (ISR) and restore cellular homeostasis via the transcription factor ATF4. However, under persistent stress, ATF4 induces CHOP, shifting the adaptive response toward apoptosis. PKR, also activated by ER stress, phosphorylates eIF2, but its contribution to cellular homeostasis remains understudied. This work shows, for the first time, that PKR activation is essential for CHOP induction during ISR, directly linking enhanced apoptosis in DYT-PRKRA cells to prolonged PKR activation and heightened CHOP induction. Strikingly, a small-molecule PKR inhibitor effectively blocks CHOP expression and significantly decreases apoptosis in DYT-PRKRA cells, suggesting PKR inhibition as an effective therapeutic strategy for DYT-PRKRA.

molecular biology↗