Biology subjects

Yu, H.-G.

Publications and source records attributed to Yu, H.-G..

4 recordsLinked to original sources

bioRxiv2025

The inner nuclear membrane-associated protein Csa1 regulates lipid droplet biogenesis and nuclear shape in a Sir2-dependent manner

The nuclear envelope, a double-membrane structure consisting of the inner nuclear membrane (INM) and the outer nuclear membrane, encloses the nucleus. In response to cellular cues, lipid droplets are formed at the INM, which plays a key role in membrane homeostasis and energy storage. However, the signaling pathway that regulates the formation of nuclear lipid droplets remains to be elucidated. Here we show that in budding yeast, the INM-localized protein Csa1 regulates the nuclear localization of the acyltransferase Lro1, which converts diacylglycerol to triacylglycerol, leading to lipid droplet formation. Csa1 harbors a bipartite nuclear localization signal for nuclear sorting, along with an amphipathic helix that anchors it to the INM. Upon nutrient depletion and at the onset of meiosis, both Csa1 and Lro1 are enriched at a distinct INM subdomain that abuts the nucleolus, which we term the n-INM. We show that Csa1 is essential for targeting Lro1 to the n-INM region. In the absence of Csa1, Lro1 is dispersed along the nuclear periphery. The deacetylase activity of Sir2 is required for the n-INM enrichment of both Csa1 and Lro1. In the absence of either Csa1 or Sir2, lipid droplet formation is compromised. Our findings uncover an unexpected Sir2-dependent Csa1-Lro1 signaling pathway at the INM that regulates lipid droplet biogenesis and nuclear envelope remodeling.

cell biology↗

bioRxiv2021

Pseudouridine-free Ribosome Exhibits Distinct Inter-subunit Movements

Pseudouridine, the most abundant form of RNA modification, is known to play important roles in ribosome function. Mutations in human DKC1, the pseudouridine synthase responsible for catalyzing the ribosome RNA modification, cause translation deficiencies and are associated with a complex cancer predisposition. The structural basis for how pseudouridine impacts ribosome function remains uncharacterized. Here we report electron cryomicroscopy structures of a fully modified and a pseudouridine-free ribosome from Saccharomyces cerevisiae. In the modified ribosome, the rearranged N1 atom of pseudouridine is observed to stabilize key functional motifs by establishing predominately water-mediated close contacts with the phosphate backbone. The pseudouridine-free ribosome, however, is devoid of such interactions and displays conformations reflective of abnormal inter-subunit movements. The erroneous motions of the pseudouridine-free ribosome may explain its observed deficiencies in translation.

biochemistry↗

bioRxiv2020

Mps2 links Csm4 and Mps3 to form a telomere-associated LINC complex in budding yeast

The linker of the nucleoskeleton and cytoskeleton (LINC) protein complex is composed of a pair of transmembrane proteins: the KASH-domain protein localized to the outer nuclear membrane and the SUN-domain protein to the inner nuclear membrane. In budding yeast, the sole SUN-domain protein, Mps3, is thought to pair with either Csm4 or Mps2, two KASH-like proteins, to form two separate LINC complexes. Here we show that Mps2 mediates the interaction between Csm4 and Mps3 to form a heterotrimeric telomere-associated LINC (t-LINC) in budding yeast meiosis. Mps2 binds to Csm4 and Mps3, and all three are localized to the telomere. Telomeric localization of Csm4 depends on both Mps2 and Mps3; in contrast, Mps2s localization depends on Mps3 but not Csm4. Mps2-mediated t-LINC regulates telomere movement and meiotic recombination. By ectopically expressing CSM4 in vegetative yeast cells, we reconstitute the heterotrimeric t-LINC and demonstrate its ability to tether telomeres. Our findings therefore reveal the heterotrimeric composition of t-LINC in budding yeast and have implications for understanding LINC variant formation.

cell biology↗

bioRxiv2018

The anaphase-promoting complex regulates the degradation of the inner nuclear membrane protein Mps3 in budding yeast

The nucleus is enclosed by the inner nuclear membrane (INM) and the outer nuclear membrane (ONM). While the ONM is continuous with the endoplasmic reticulum (ER), the INM is independent and separates the nucleoplasm from the ER lumen. To maintain INM homeostasis, proteins mislocalized to the INM are degraded by the ER-associated protein degradation (ERAD) pathway. However, the mechanism for turnover of resident INM proteins is less clear. Here we show that the anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase, regulates the degradation of Mps3, a conserved integral protein of the INM. Turnover of Mps3 requires the ubiquitin-conjugating enzymes Ubc7 and Ubc6, but not the three known ERAD ubiquitin ligases, Doa10, Hrd1, and the Asi1-Asi3 complex. Using a genetic approach, we have found that Cdh1, a coactivator of APC/C, modulates Mps3 stability. APC/C controls Mps3 degradation through Mps3s N-terminus, which resides in the nucleoplasm and possesses two putative APC/C-dependent destruction motifs. Accumulation of Mps3 at the INM impairs nuclear morphological changes and cell division. Our findings therefore reveal an unexpected mechanism of APC/C-mediated protein quality control at the INM that coordinates nuclear morphogenesis and cell-cycle progression.

cell biology↗