Biology subjects

Yan, Y.-H.

Publications and source records attributed to Yan, Y.-H..

6 recordsLinked to original sources

bioRxiv2026

Selective activation of IRE-1 safeguards restoration of translation and organismal rejuvenation from adult reproductive diapause

In C. elegans, prolonged food deprivation during early larval development results in aging-like phenotypes that can be fully reversed upon refeeding, but it remains unknown whether and how this ability persists into later life stages. Here we subjected C. elegans of the last larval stage to starvation, driving them into adult reproductive diapause (ARD). During starvation, ARD worms exhibited a wide spectrum of aging-like phenotypes, including transcriptomic reprogramming accompanying cellular and functional declines. These phenotypes are largely restored within one day of refeeding, suggesting a rejuvenation effect. Time-series transcriptomics, proteomics, and follow-up analyses of the refeeding/rejuvenation process uncovered an intricate coordination between: (1) activation of the IRE-1 branch of UPRER (unfolded protein response of endoplasmic reticulum) to induce chaperone expression; (2) quiescence of the PEK-1 branch of UPRER to avoid translation suppression; (3) up-regulation of the translation machinery to boost protein synthesis. IRE-1, together with its downstream effector, XBP-1, play an essential role in boosting protein synthesis, which is required for complete rejuvenation from the ARD state. These findings indicate that coordination between a high protein synthesis activity and a high protein folding capacity is key to refeeding-associated rejuvenation. HighlightsO_LIRefeeding rapidly reverses aging-like phenotypes in adult reproductive diapause C_LIO_LIRefeeding selectively activates the IRE-1 branch of UPRER C_LIO_LIRefeeding restores protein synthesis in an IRE-1 dependent manner C_LIO_LIRejuvenation requires enhanced translation activity and protein folding capacity C_LI

cell biology↗

bioRxiv2026

Dual Inhibition of MYRF Cleavage by Its JM Region and PAN-1 CCT Gates Developmental Timing in C. elegans

Post-embryonic development proceeds through discrete stages, yet the mechanisms that coordinate transitions between stages remain incompletely defined. The transmembrane transcription factor MYRF undergoes intramolecular cleavage to release a nuclear-localized fragment essential for developmental progression in C. elegans. Previously, we showed that PAN-1 as a key partner required for MYRF activity during development. PAN-1 promotes MYRF trafficking to the cell membrane--an essential step for MYRF cleavage--through interactions between their extracellular domains (Xia et al., 2021). Here, we show that MYRF-1 cleavage and nuclear translocation oscillate with larval stage transitions in C. elegans, peaking mid-to-late stage and being suppressed during molts. Using endogenous gene editing and mutant reporters, we identify an uncharacterized juxtamembrane (JM) region in MYRF-1 that self-inhibits cleavage. JM deletion triggers premature MYRF-1 nuclear entry, early lin-4 activation, growth defects, and adult lethality. We further demonstrate that the cytoplasmic tail (CCT) of the transmembrane protein PAN-1 acts as a predominant trans-inhibitor of MYRF-1 cleavage, coupling extracellular association with cytoplasmic inhibition. PAN-1 CCT deletion causes near-constitutive MYRF-1 nuclear accumulation, leading to premature lin-4 activation, accelerated M-cell division, and larval lethality. Removing these inhibitory mechanisms on MYRF-1 cleavage overrides nutrient-responsive developmental checkpoints. These findings uncover dual inhibitory mechanisms governing MYRF-1 cleavage and establish MYRF-1 cleavage as a key gatekeeper of developmental timing.

developmental biology↗

bioRxiv2022

A family of C. elegans VASA homologs control Argonaute pathway specificity and promote transgenerational silencing

Germline Argonautes direct transcriptome surveillance within peri-nuclear membraneless organelles called nuage. In C. elegans, a family of Vasa-related Germ Line Helicase (GLH) proteins localize in, and promote the formation of nuage called P granules. Previous studies have implicated GLH proteins in inherited silencing but direct roles in amplification of small RNAs, or in target mRNA or Argonatue binding have not been identified. Here we show that GLH proteins compete with each other to control Argonaute pathway specificity, bind directly to Argonaute-target mRNAs and act to promote the amplification of small RNAs required for transgenerational inheritance. We show that the ATPase cycle of GLH-1 regulates its direct binding to the Argonaute WAGO-1 which engages amplified small RNAs. Our findings support a dynamic and direct role for GLH proteins in inherited silencing beyond their role as structural components of nuage.

molecular biology↗

bioRxiv2020

HDAC1 SUMOylation promotes Argonaute directed transcriptional silencing in C. elegans

Eukaryotic cells use guided search to coordinately control dispersed genetic elements. The transitive effectors of these mechanisms, Argonaute proteins and their small-RNA co-factors, engage nascent RNAs and chromatin-associated proteins to direct transcriptional silencing. The small ubiquitin-like modifier (SUMO) has been shown to promote the induction and maintenance of silent chromatin (called heterochromatin) in yeast, plants, and animals. Here we show that Argonaute-directed transcriptional silencing in C. elegans requires SUMOylation of the type 1 histone deacetylase HDA-1. SUMOylation of HDA-1 promotes interactions with components of the nucleosome remodeling and deacetylase (NuRD) complex and with the nuclear Argonaute HRDE-1/WAGO-9. Our findings suggest how HDAC1 SUMOylation promotes the association of HDAC and other chromatin remodeling factors with a nuclear Argonaute in order to initiate de novo heterochromatin silencing.

molecular biology↗

bioRxiv2018

Differential phase partition of a PICS complex is required for piRNA processing and chromosome segregation in C. elegans

Piwi-interacting RNAs (piRNAs) play significant roles in suppressing transposons and non-self nucleic acids, maintaining genome integrity, defending against viral infections, and are essential for fertility in a variety of organisms. In C. elegans, most piRNA precursors are transcribed by RNA polymerase II in the nucleus and are subjected to a number of processing and maturation steps. However, the biogenesis of piRNAs are still not fully understood. We used functional proteomics to study piRNA biogenesis in C. elegans and identified a PICS complex that is required for piRNA processing and chromosome segregation. The PICS complex contains two known piRNA biogenesis factors TOFU-6 and PID-1, and three new proteins PICS-1, TOST-1, and ERH-2, which exhibit dynamic localization among different subcellular compartments. In the germline of gravid animals, the PICS complex contains TOFU-6/PICS-1/ERH-2/PID-1 and largely concentrate at the perinuclear granule zone and engages in piRNA processing. During early embryogenesis, the TOFU-6/PICS-1/ERH-2/TOST-1 complex accumulates in the nucleus and play essential roles in chromosome segregation and cell division. Interestingly, the function of these factors in mediating chromosome segregation is independent of piRNA production. Therefore, we speculate that a differential phase partition of PICS factors may help cells to coordinate distinct cellular processes.

genetics↗

bioRxiv2018

The USTC complex co-opts an ancient machinery to drive piRNA transcription in C. elegans

Piwi-interacting RNAs (piRNAs) engage Piwi proteins to suppress transposons and non-self nucleic acids, maintain genome integrity, and are essential for fertility in a variety of organisms. In C. elegans most piRNA precursors are transcribed from two genomic clusters that contain thousands of individual piRNA transcription units. While a few genes have been shown to be required for piRNA biogenesis the mechanism of piRNA transcription remains elusive. Here we used functional proteomics approaches to identify an upstream sequence transcription complex (USTC) that is essential for piRNA biogenesis. The USTC complex contains PRDE-1, TOFU-4, TOFU-5 and SNPC-4. The USTC complex form a unique piRNA foci in germline nuclei and coat the piRNA cluster genomic loci. USTC factors associate with the Ruby motif just upstream of type I piRNA genes. USTC factors are also mutually dependent for binding to the piRNA clusters and to form the piRNA foci. Interestingly, USTC components bind differentially to piRNAs in the clusters and other non-coding RNA genes. These results reveal USTC as a striking example of the repurposing of a general transcription factor complex to aid in genome defence against transposons.

developmental biology↗