Biology subjects

Ketting, R. F.

Publications and source records attributed to Ketting, R. F..

At least 19 recordsLinked to original sources

bioRxiv2026

Phosphorylation of Z granule components regulates germ granule organization and RNAi inheritance

Small RNAs represent important carriers of epigenetic information in nematodes, and factors involved in their biogenesis reside within perinuclear germ granules. Among these condensates, Z granules are essential for the inheritance of RNA interference (RNAi). The mechanisms by which Z granules form and promote this process remain unclear. We show that Casein kinase I alpha (KIN-19) is present in Z granules and associated with DEPS-1 and HERD-1 phosphorylation. In the absence of DEPS-1 and HERD-1 phosphorylation, animals have enlarged Z granules and enhanced RNAi inheritance. We propose that DEPS-1 acts as a phosphorylation-regulated scaffold that bridges ZNFX-1 and HERD-1 proteins. Our study demonstrates that Casein kinase I alpha-mediated phosphorylation is an important factor in germ granule modulation and RNAi inheritance, and additionally provides a novel molecular scaffold for understanding germ granule complexity in C. elegans.

molecular biology↗

bioRxiv2026

A pseudohelicase-centered complex couples assembly-dependent RNA cleavage to poly(UG)ylation

Robust RNA interference in Caenorhabditis elegans requires Argonaute targeted RNAs to be cleaved by RDE 8 and poly(UG)ylated by MUT 2, generating templates for RNA dependent RNA polymerases that synthesize secondary small RNAs. RDE 8 and MUT 2 are physically coupled within the cleavage and poly(UG)ylation (CPUG) complex, together with the pseudonuclease NYN 1 and MUT 15, but how their activities are controlled and coordinated is unknown. Structural and biochemical analyses reveal that the RDE 8/NYN 1 nuclease module is autoinhibited, restricting cleavage outside CPUG. We identify MUT 15, the CPUG scaffold linking this nuclease module to MUT 2, as a pseudohelicase. MUT 15 remodels the nuclease module, licensing RDE 8 activity upon complex assembly. Reconstituted CPUG synthesizes long poly(UG) tails, with the substrate 3' end determining tailing efficiency and register. Within CPUG, RNA engagement by MUT 2 limits RDE 8 access, while poly(UG) tails themselves are not cleaved by RDE 8, preventing re cleavage. Together, CPUG couples assembly dependent RNA cleavage to downstream processing, imposing safety and directionality.

biochemistry↗

bioRxiv2026

Atomistic simulations reveal sub-μs contact dynamics in MUT-16 condensates.

Phase separation of proteins gives rise to biomolecular condensates, which function as membraneless organelles that spatially and temporally organize cellular functions. Such condensates are often formed by intrinsically disordered regions of proteins (IDRs), whose multivalent and transient interactions govern condensate structure and dynamics. However, elucidating the molecular determinants of these interactions at atomistic resolution remains challenging. Here, we present a total of 10 {micro}s of atomistic molecular dynamics simulations of a phase-separated condensate formed by the foci-forming region (FFR) of MUT-16. MUT-16 serves as a scaffold of the Mutator foci germ granules in Caenorhabditis elegans and is essential for transposon silencing. MUT-16 FFR is enriched in polar uncharged (Gln, Asn), charged, aromatic, and Pro residues, raising the question of how these amino acids interact within condensates. We find that most contacts are short lived, typically breaking within a few nanoseconds (ns), with a median life time of 9.8 ns. A smaller fraction persist for much longer timescales (> 100 ns). We characterized the relative contributions of different amino acids and specific interaction types, including hydrogen bonding, cation-{pi} interactions,{pi} -{pi} stacking, and salt bridges and theirs dynamics. We further examined the roles of water and ions in modulating condensate interactions, including ion-mediated bridging between similarly charged residues. Our results reveal that salt bridges, cation-{pi} interactions, Na+ ions, and water in the condensate are key determinants of contact dynamics in MUT-16 FFR condensates. In parallel, we show that these condensates exhibit upper-critical solution temperature (UCST) phase behavior in vitro, providing a coherent framework to explain both the loss of Mutator foci at elevated temperatures in vivo and the scaffolding role of MUT-16 at lower temperatures.

biochemistry↗

bioRxiv2026

SLBP-independent control of maternal histone mRNA

Replication-dependent (RD) histones are crucial for packaging newly replicated DNA into chromatin, ensuring genome stability. In metazoans, the mRNA of RD histones is uniquely regulated through a conserved 3' stem-loop bound by stem-loop binding protein (SLBP). This allows cell cycle-coupled regulation of these important transcripts. However, oocytes must stabilise histone mRNAs independently of the cell cycle to ensure maternal loading to support the first embryonic divisions. Using Caenorhabditis elegans as a model system, we discovered an SLBP-independent mechanism that ensures RD histone transcript stability during oogenesis. This is mediated by the protein complex PETISCO, bound to the effector protein TOST-1, which directly binds the histone stem-loop region and maintains maternal histone mRNA levels during oogenesis and early embryogenesis. Loss of this mechanism disrupts histone homeostasis, leading to premature genome activation, mitotic defects, and embryonic lethality. Interestingly, the same complex, PETISCO, acts in piRNA biogenesis when bound to the effector PID-1, revealing an intriguing co-option of this histone mRNA homeostasis mechanism by the piRNA pathway. Our findings reveal a unique SLBP-independent mechanism of histone mRNA regulation, that served as a basis for the evolution of a novel piRNA biogenesis mechanism.

molecular biology↗

bioRxiv2025

An Evolutionarily Conserved N-terminal Domain of RRF-3 Governs GTSF-1 Binding in Nematodes

GTSF1 is an essential activating cofactor for PIWI proteins in many metazoans. In the nematode Caenorhabditis elegans, however, GTSF-1 does not bind PIWI, but associates with the RNA-dependent RNA polymerase RRF-3, supporting endo-siRNA (26G-RNA) biogenesis. Here, we demonstrate that this rewiring is deeply conserved across nematodes. For C. briggsae and Pristionchus pacificus we show that GTSF-1 interacts with RRF-3 and is essential for 26G-RNA production and fertility. We map this interaction to an N-terminal domain of RRF-3, termed the GTSF-1 interacting domain (GID), and show that the GTSF-1 zinc finger region alone is sufficient for binding. Mutagenesis identifies critical residues mediating this interaction and reveals that GTSF-1 stability depends on RRF-3. Other RdRPs possess GID-like domains, which we propose to bind GTSF-1-related proteins. Phylogenomic and structural analyses support GTSF-1-RRF-3 interactions across all major nematode lineages and map the shift in GTSF-1 activity to the last common nematode ancestor. We propose that binding of GTSF-1 induces conformational changes in RRF-3 that facilitate ERI complex assembly and activate RdRP function, paralleling its role as a PIWI activator.

molecular biology↗

bioRxiv2025

Proteolytic Control of an Auto-inhibitory Intrinsically Disordered Region Governs Small RNA Selectivity in Argonaute Proteins

Argonaute proteins are central to small RNA-mediated gene regulation, yet the mechanisms controlling their activity remain incompletely understood. We elucidate a novel regulatory mechanism governing small RNA loading into the C. elegans Argonaute proteins WAGO-1 and WAGO-3. We show that N-terminal intrinsically disordered regions (N-IDRs) of these proteins do not affect subcellular localization but play critical roles in small RNA loading. We demonstrate that the N-IDR-processing protease DPF-3 facilitates small RNA loading in a catalysis-independent manner. Catalysis by DPF-3 and a second protease APP-1 is required, however, for activity. Deletion of these N-IDRs results in loading of aberrant small RNA species that trigger erroneous gene silencing. Supported by atomistic molecular dynamics simulations, we propose a model in which N-IDRs can simultaneously act as tuneable gatekeepers that auto-inhibit small RNA loading and as regulators of Argonaute stability, representing a previously unrecognized layer of regulation in Argonaute activity in small RNA pathways.

molecular biology↗

bioRxiv2025

Crosstalk between and developmental dynamics of C. elegans Argonaute proteins

Gene regulation via Argonaute-bound small RNAs is a broadly conserved mechanism, present in all domains of life. The nematode Caenorhabditis elegans expresses several worm-specific Argonautes (WAGOs), which interact with the small RNAs known as 22G-RNAs. These WAGOs have roles in gene regulation, transposon-defence as well as in viral control and experimentally induced RNA interference. Despite many studies, direct relationships between WAGO targeting, as defined by 22G RNA sequences, and mRNA abundance are not clear. Also, the effects of developmental stage and WAGO-interconnectivity have been under-studied thus far. We studied these aspects for two germline-expressed WAGO proteins, WAGO-1 and WAGO-3. We show that WAGO-1 mostly affects 22G-RNA expression in gravid adult worms, while WAGO-3 predominantly affects 22G-RNA expression in embryos. Furthermore, we detect a link between WAGO-3 and the maternal 26G-RNA pathway governed by the Argonaute protein ERGO-1, and between WAGO-1 and the paternal 26G-RNA pathway governed by the Argonautes ALG-3/4. We also demonstrate that, globally speaking, loss of WAGO-1 or WAGO-3 does not result in upregulation of their target mRNAs, as defined by 22G-RNA complementarity. Finally, metagene analysis of 22G-RNA profiles suggests loss of one WAGO protein leads to shifts in WAGO 22G-RNA binding. Overall, we conclude that WAGO-1 and WAGO-3 are developmentally dynamic, are embedded in distinct regulatory networks, and that potential silencing of individual mRNAs by these WAGO proteins is hard to assess by simple loss-of-function studies. SummaryRNA interference describes silencing of genes via small RNAs coupled to an Argonaute protein. C. elegans expresses a class of secondary small RNAs known as 22G-RNAs which are coupled to Argonautes known as WAGOs (worm-specific Argonautes). We have sequenced 22G-RNA and mRNA populations from deletion mutants of two such WAGOs, WAGO-1 and WAGO-3, to investigate Argonaute crosstalk and the relationship between 22G-RNA and mRNA levels. We found that WAGO-1 and WAGO-3 engage different, complementary pathways, and that target silencing cannot be deduced simply from 22G-RNA complementarity.

genetics↗

bioRxiv2024

Meioc-Piwil1 complexes regulate rRNA transcription for differentiation of spermatogonial stem cells

Ribosome biogenesis is vital for sustaining stem cell properties, yet its regulatory mechanisms are obscure. Herein, we show unique properties of zebrafish meioc mutants in which spermatogonial stem cells (SSCs) do not differentiate or upregulate rRNAs. Meioc colocalized with Piwil1 in perinuclear germ granules, but Meioc depletion resulted in Piwil1 accumulation in nucleoli. Nucleolar Piwil1 interacted with 45S pre-rRNA. piwil1+/-spermatogonia with reduced Piwil1 upregulated rRNAs, and piwil1+/-;meioc-/- spermatogonia recovered differentiation later than those in meioc-/-. Further, Piwil1 interacted with Setdb1 and HP1, and meioc-/- spermatogonia exhibited high levels of H3K9me3 and methylated CpG in the 45S-rDNA region. These results indicate that zebrafish SSCs maintain low levels of rRNA transcription with repressive marks similar to Drosophila piRNA targets of RNA polymerase II, and that Meioc has a unique function on preventing localization of Piwil1 in nucleoli to upregulate rRNA transcripts and to promote SSC differentiation.

developmental biology↗

bioRxiv2024

Germplasm stability in zebrafish requires maternal Tdrd6a and Tdrd6c

Germ cell specification is driven, in many species, by germplasm: a collection of phase-separation-based structures in the embryo, formed by RNA and proteins that derive from the cytoplasm of the oocytes. How the formation of germplasm is regulated, especially in vertebrates, remains unclear. In this study, we show that two multi-Tudor proteins, Tdrd6a and Tdrd6c, together are necessary for the stability of germplasm in zebrafish, while the related Balbiani body in the oocyte is largely unaffected. Combined lack of maternal Tdrd6a and Tdrd6c still allows the initial germplasm formation but causes its dispersal during the first hours of development. This results in the absence of primordial germ cells during later development and in sterility of the resulting adult animals. Furthermore, our study suggests that the Prion-like domain of Tdrd6c is relevant for Tdrd6c self-interaction as well as for its interaction with Bucky ball, the organizer of germplasm in zebrafish and that these dynamics are modulated by Tdrd6c Tudor domains. The identification of Tdrd6a and Tdrd6c as required for germplasm stability is an important step in our understanding of how this phase-separated structure is controlled during development. Author SummaryWe show that maternal Tdrd6a and Tdrd6c proteins interact with Bucky Ball and are essential for embryonic germplasm stability, germ cell specification and fertility in zebrafish.

developmental biology↗

bioRxiv2024

A genetic framework for RNAi inheritance in Caenorhabditis elegans

Gene regulation by RNA interference (RNAi) is a conserved process driven by double-stranded RNA (dsRNA). It responds to exogenous cues and drives endogenous gene regulation. In Caenorhabditis elegans, RNAi can be inherited from parents to offspring. While a number of factors have been implicated in this inheritance process, we do not understand how and when they function. Using a new inheritance assay, we establish a hierarchy amongst previously identified inheritance factors. The nuclear argonaute protein HRDE-1 was required for RNAi establishment in parents and offspring, but not for the inheritance process. In contrast, the cytoplasmic argonaute protein WAGO-3 was the only factor essential for inheritance, via sperm and oocyte, while not affecting establishment in either parent or offspring. We propose a cycle between nuclear and cytoplasmic argonaute proteins, where nuclear activity drives most of the silencing and cytoplasmic activity ensures inheritance. Finally, we implicate the RNA helicase ZNFX-1 as a factor that controls the entry of exogenous versus endogenous small RNAs into this cycle, ensuring a proper balance between gene silencing and activity.

genetics↗

bioRxiv2024

Regulation of Microprocessor assembly and localization via Pasha's WW domain in C. elegans

Primary microRNA (pri-miRNA) transcripts are processed by the Microprocessor, a protein complex that includes the ribonuclease Drosha and its RNA binding partner DGCR8/Pasha. We developed a live, whole animal, fluorescence-based sensor that reliably monitors pri-miRNA processing with high sensitivity in C. elegans. Through a forward genetic selection for alleles that desilence the sensor, we identified a mutation in the conserved G residue adjacent to the namesake W residue of Pashas WW domain. Using genome editing we also mutated the W residue and reveal that both the G and W residue are required for dimerization of Pasha and proper assembly of the Microprocessor. Surprisingly, we find that the WW domain also facilitates nuclear localization of Pasha, which in turn promotes nuclear import or retention of Drosha. Furthermore, depletion of Pasha or Drosha causes both components of the Microprocessor to mislocalize to the cytoplasm. Thus, Pasha and Drosha mutually regulate each others spatial expression in C. elegans.

molecular biology↗

bioRxiv2024

Multiscale simulations of molecular recognition by phase separated MUT-16: A scaffolding protein of Mutator foci

Phase separation of proteins plays a critical role in cellular organisation. How phase separated protein condensates underpin biological function and how condensates achieve specificity remain elusive. We investigated the phase separation of MUT-16, a scaffold protein in Mutator foci, and its role in recruiting the client protein MUT-8, a key component in RNA silencing in C. elegans. We employed a multiscale approach that combined coarse-grained (residue-level CALVADOS2 and near-atomistic Martini3) and atomistic simulations. Simulations across different resolutions provide a consistent perspective on how MUT-16 condensates recruit MUT-8, enabling the fine-tuning of chemical details while balancing the computational cost. Both coarse-grained models (CALVADOS2 and Martini3) predicted the relative phase separation propensities of MUT-16s disordered regions, which we confirmed through in vitro experiments. Simulations also identified key sequence features and residues driving phase separation while revealing differences in residue interaction propensities between CALVADOS2 and Martini3. Furthermore, Martini3 and 350 {micro}s atomistic simulations on Folding@Home of MUT-8s N-terminal prion-like domain with MUT-16 M8BR cluster highlighted the importance of cation-{pi} interactions between Tyr residues of MUT-8 and Arg residues of MUT-16 M8BR. Lys residues were observed to be more prone to interact in Martini3. Atomistic simulations revealed that the guanidinium group of Arg also engages in sp2-{pi} interactions and hydrogen bonds with the backbone of Tyr, making Arg-Tyr interactions stronger than Lys-Tyr, where these additional favourable contacts are absent. In agreement with our simulations, in vitro co-expression pulldown experiments demonstrated a progressive loss of MUT-8 recruitment following the mutation of Arg in MUT-16 M8BR to Lys or Ala, confirming the critical role of Arg in this interaction. These findings advance our understanding of MUT-16 phase separation and subsequent MUT-8 recruitment, key processes in assembling Mutator foci that drive RNA silencing in C. elegans. Statement of SignificanceIn cells proteins phase separate and form condensates. These protein condensates can play important role in bringing molecules together and facilitate biochemical processes. In this work, we used molecular dynamics simulations to understand how MUT-16 phase separates and forms the scaffold of the so-called Mutator focus. Mutator foci produce small RNA which help to regulates genes. As the scaffold of the Mutator focus, MUT-16 recruit multiple proteins which are important for the production of such small RNAs.

bioinformatics↗

bioRxiv2023

MUT-7 exoribonuclease activity and localisation are mediated by an ancient domain

The MUT-7 family of 3-5 exoribonucleases is evolutionarily conserved across the animal kingdom and plays essential roles in small RNA production in the germline. Most MUT-7 homologs carry a C-terminal domain of unknown function named MUT7-C appended to the exoribonuclease domain. Our analysis shows that the MUT7-C is evolutionary ancient, as a minimal version of the domain exists as an individual protein in prokaryotes. In animals, MUT7-C has acquired an insertion that diverged during evolution, expanding its functions. C. elegans MUT-7 contains a specific insertion within MUT7-C, which allows binding to MUT-8 and, consequently, MUT-7 recruitment to germ granules. In addition, in C. elegans and human MUT-7, the MUT7-C domain contributes to RNA binding and is thereby crucial for nuclease activity. This RNA-binding function most likely represents the ancestral function of the MUT7-C domain. Overall, this study sheds light on MUT7-C and assigns two functions to this previously uncharacterised domain.

biochemistry↗

bioRxiv2023

Age- and caste-independent piRNAs in the germline and miRNA profiles linked to caste and fecundity in the ant Temnothorax rugatulus

Social insects are models for phenotypic plasticity: the generation of different phenotypes from the same genotype. Ant queens and workers differ not only in their morphology and behaviour, but also in their fecundity and lifespan, which is often several times higher in queens. However, the gene regulatory mechanisms underlying these differences are not yet well understood. Since ant queens can live and reproduce for more than two decades, they need to protect their germline from the activity of transposable elements (TEs). This protection may be redundant in short-lived, often sterile workers. We have analysed the expression of two protective classes of smallRNAs, microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs), in different tissues, castes, and age classes of the ant species Temnothorax rugatulus. We show that piRNAs are particularly active in the ovaries of queens. TEs are clear targets of the piRNAs in this ant species, and piRNA-specific sequence signatures in the ovaries of all queens regardless of age indicate that young and old queens have similarly active piRNA pathways. Interestingly, the reduced ovaries of the workers also showed the same level of piRNA activity. This was not only the case in young, fertile workers from queenless nests, but also in the presumably older foragers, which have almost completely regressed ovaries. These findings suggest that the germline in these ants is invariably protected by piRNA activity, irrespective of ovarian development. The brain and thorax of queens also contained piRNAs, but at lower levels, and the piRNA-specific ping-pong signatures were strongly reduced in these tissues. We also annotated and analysed miRNAs in different tissues. We confidently detected the expression of 304 miRNAs. Of these, 10 were enriched in the brain and three to the thorax, whereas 83 were specific to the ovaries. 105 miRNAs were found to be expressed in all three tissues. We also identified miRNAs whose expression potentially is related to ant caste, fecundity, and age, suggesting that caste-specific gene activity may be regulated in part by miRNAs. In contrast, our studies of piRNA activity indicate similar profiles across caste, fecundity and age groups, but strong tissue specificity with the highest piRNA mediated TE protection in the germline.

ecology↗

bioRxiv2023

An extended Tudor domain within Vreteno interconnects Gtsf1L and Ago3 for piRNA biogenesis in Bombyx mori

Piwi-interacting RNAs (piRNAs) direct PIWI proteins to transposons to silence them, thereby preserving genome integrity and fertility. The piRNA population can be expanded in the ping-pong amplification loop. Within this process, piRNA-associated PIWI proteins (piRISC) enter the nuage to cleave target RNA, which is stimulated by Gtsf proteins. The resulting cleavage product gets loaded into an empty PIWI protein to form a new piRISC complex. However, for piRNA amplification to occur, it is required that new RNA substrates, Gtsf-piRISC and empty PIWI proteins are all in physical proximity. In this study we show that BmGtsf1L binds to piRNA-loaded BmAgo3 and co-localizes to BmAgo3-BmVreteno positive granules. Biochemical assays further revealed that conserved residues within the unstructured tail of BmGtsf1L directly interact with BmVreteno. Using a combination of AlphaFold modeling, atomistic molecular dynamics simulations and in vitro assays we identified a novel binding interface on a BmVreteno-eTudor domain, which is required for BmGtsf1L binding. Our study reveals that a single eTudor domain within BmVreteno provides two binding interfaces and thereby interconnects piRNA-loaded BmAgo3 and BmGtsf1L.

molecular biology↗

bioRxiv2021

Maternally-inherited anti-sense piRNAs antagonize transposon expression in teleost embryos

Transposable elements threaten genome stability, and the Piwi-piRNA system has evolved to silence transposons in the germline1-6. However, it remains largely unknown what mechanisms are utilized in early vertebrate embryos prior to germline establishment and ping-pong piRNA production. To address this, we first characterized small RNAs in early zebrafish embryos and detected abundant maternally-deposited, Ziwi-associated, antisense piRNAs that map largely to evolutionarily young long terminal repeat (LTR) retrotransposons. Notably, the focal establishment of the repressive modification H3K9me2/3 coincides with these young LTR elements, is deposited independent of transcription, and is required for LTR silencing. We find piRNAs highly enriched and maintained in primordial germ cells (PGCs), which display lower LTR expression than somatic cells. To examine the consequences of piRNA loss, we used reciprocal zebrafish-medaka hybrids, which display selective activation of LTRs that lack maternally-contributed targeting piRNAs. Thus, the Piwi-piRNA system actively antagonizes transposons in the soma and PGCs during early vertebrate embryogenesis.

developmental biology↗

bioRxiv2021

Structural basis of PETISCO complex assembly during piRNA biogenesis in C. elegans

Piwi-interacting RNAs (piRNAs) constitute a class of small RNAs that bind PIWI proteins and are essential to repress transposable elements in the animal germline, thereby promoting genome stability and maintaining fertility. C. elegans piRNAs (21U RNAs) are transcribed individually from minigenes as precursors that require 5 and 3 processing. This process depends on the PETISCO complex, consisting of four proteins: IFE-3, TOFU-6, PID-3, and ERH-2. We employ biochemical and structural biology approaches to characterize the PETISCO architecture and its interaction with RNA, together with its effector proteins TOST-1 and PID-1. These two proteins define different PETISCO functions: PID-1 governs 21U processing whereas TOST-1 links PETISCO to an unknown process essential for early embryogenesis. Here, we show that PETISCO forms an octameric assembly with each subunit present in two copies. Determination of structures of the TOFU-6/PID-3 and PID-3/ERH-2 subcomplexes, supported by in vivo studies of subunit interaction mutants, allows us to propose a model for the formation of the TOFU-6/PID-3/ERH-2 core complex, and its functionality in germ cells and early embryos. Using NMR spectroscopy, we demonstrate that TOST-1 and PID-1 bind to a common surface on ERH-2, located opposite its PID-3 binding site, explaining how PETISCO can mediate different cellular roles.

biochemistry↗

bioRxiv2020

The double-stranded DNA-binding proteins TEBP-1 and TEBP-2 form a telomeric complex with POT-1

Telomeres are bound by dedicated protein complexes, like shelterin in mammals, which protect telomeres from DNA damage. In the nematode Caenorhabditis elegans, a comprehensive understanding of the proteins interacting with the telomere sequence is lacking. Here, we harnessed a quantitative proteomics approach to screen for proteins binding to C. elegans telomeres, and identified TEBP-1 and TEBP-2, two paralogs that associate to telomeres in vitro and in vivo. TEBP-1 and TEBP-2 are expressed in the germline and during embryogenesis. tebp-1 and tebp-2 mutants display strikingly distinct phenotypes: tebp-1 mutants have longer telomeres than wild-type animals, while tebp-2 mutants display shorter telomeres and a mortal germline, a phenotype characterized by transgenerational germline deterioration. Notably, tebp-1; tebp-2 double mutant animals have synthetic sterility, with germlines showing signs of severe mitotic and meiotic arrest. TEBP-1 and TEBP-2 form a telomeric complex with the known single-stranded telomere-binding proteins POT-1, POT-2, and MRT-1. Furthermore, we find that POT-1 bridges the double- stranded binders TEBP-1 and TEBP-2, with the single-stranded binders POT-2 and MRT-1. These results describe the first telomere-binding complex in C. elegans, with TEBP-1 and TEBP-2, two double-stranded telomere binders required for fertility and that mediate opposite telomere dynamics.

cell biology↗