Biology subjects

zheng, H.

Publications and source records attributed to zheng, H..

3 recordsLinked to original sources

bioRxiv2026

Plant-specific and conserved mechanisms of the polymerase-associated factor 1 complex in replication stress responses

DNA replication stress threatens genome stability in eukaryotes. The evolutionarily conserved kinase WEE1 is essential for the activation of the replication stress response. Although the polymerase-associated factor 1 complex (PAF1C) is highly conserved in eukaryotes, its role in the DNA replication stress response remains unclear. Here, we show that Arabidopsis PAF1C is essential for replication stress response. PAF1C-deficient mutants exhibit hypersensitivity to hydroxyurea (HU)-induced replication stress. Mechanistically, we uncover a plant-specific regulatory pathway in which WEE1 interacts with and phosphorylates the PAF1 subunit within its unique N-terminal domain, thereby preventing PAF1 polyubiquitination and subsequent proteasomal degradation to ensure PAF1 accumulation under stress. Genetically, overexpression of a phospho-mimetic PAF1 variant suppresses the HU hypersensitivity of wee1, revealing that PAF1 acts downstream of WEE1. However, the WEE1-PAF1 regulatory axis is absent in yeast, indicating its lineage-specific innovation. Further studies reveal that the replication factor C (RFC) complex interacts with and recruits PAF1 to the stalled replication forks. PAF1 then sequentially recruits the E2 ubiquitin-conjugating enzymes UBC1/2 and the E3 ubiquitin ligases HUB1/2 to promote histone H2B monoubiquitination (H2Bub), thereby facilitating replication fork stability. This RFC-dependent recruitment mechanism is conserved in yeast. Collectively, this study suggests that PAF1 regulates replication stress responses by integrating a plant-specific protein stability control mechanism (WEE1-PAF1) with a conserved recruitment mechanism (RFC-PAF1-UBC1/2-HUB1/2), uncovering a novel function of PAF1C and revealing new mechanisms of WEE1 and the RFC complex.

plant biology↗

bioRxiv2024

SlWRKY80 recruits SlHDA1 to regulates the tomato fruit ripening and color transformation

Fruit ripening involves key transcription factors (TF). Despite the established importance of WRKY TFs in plant development, the involvement of WRKY and its underlying mechanism in the regulation of fruit ripening and color transformation remain unclear. Here, we discovered a phenomenon where SlWRKY80 is involved in the ripening and color transformation of tomato. Overexpression of SlWRKY80 shortened the color transition cycle of tomato fruit, whereas loss-of-function mutation in SlWRKY80 delays this process. On the 7th day after the color breakdown (Break+7), the fruit color was bright red in SlWRKY80-overexpression lines. SlWRKY80 could bind to downstream promoters of SlSGR1 and SlPSY1, thereby exerting a positive regulatory effect on the expression levels of SlSGR1 and SlPSY1. This regulatory activity led to the facilitation of chlorophyll a decomposition and carotenoid synthesis during the transition of fruit color, ultimately accelerating fruit ripening and color change. The SlWRKY80 knockout lines (slwrky80cr-3 and slwrky80cr-4) showed light red. Thr (The 69th amino acid) mutated to Ser of SlWRKY80 (slwrky80cr-46), SlHDA1 was recruited as a regulatory factor to enhance the regulation of downstream SlPSY1 by SlWRKY80, and inhibited the SlSGR1 expression by SlWRKY80 which maybe the reason why the slwrky80cr-46 knockout lines exhibited brown color. In conclusion, SlWRKY80 regulates the expression of SlSGR1 and SlPSY1 by recruiting SlHDA1, thereby regulating chlorophyll decomposition and carotenoid synthesis, and further participating in fruit maturation and related fruit color formation. This research has important guiding significance for breeding tomato germplasm with excellent commercial traits.

plant biology↗

bioRxiv2020

LncRNA Snhg1-driven self-reinforcing regulatory network promotes cardiomyocyte cytokinesis

Most of current cardiac regenerative approaches result in very limited cell division. Positive feedback loops are vital for cell division, but their role in CM regeneration remains unclear. We aimed to demonstrate that lncRNA Snhg1 formed a positive feedback loop with c-Myc to induce stable CM cytokinesis. We found that Snhg1 expression was increased in human and mouse fetal and myocardial infarction (MI) hearts, particularly in CMs. Snhg1 overexpression elicited stable CM proliferation and improved post-MI cardiac function. Antagonism of Snhg1 in neonatal mice inhibited CM proliferation and impaired cardiac repair after MI. Proliferative effect was confirmed using cardiac-specific transgenic mice. RNA pull-down assays showed that Snhg1 directly bound to PTEN and activated PI3K-Akt pathway, resulting in c-Myc activation. Chromatin immunoprecipitation experiments showed that Snhg1 expression was upregulated by c-Myc binding to the Snhg1 promoter region, indicating a positive feedback loop between c-Myc and Snhg1. In conclusion, c-Myc/Snhg1/PI3k-Akt positive feedback loop drove sustained activation of cell cycle re-entry and induced stable CM cytokinesis, and thus may be an attractive strategy for promoting heart regenerative response. Clinical PerspectivesMost of the current cardiac regenerative approaches result in very limited cell division and little new cardiomyocyte (CM) mass. Positive feedback loops are vital for cell division, but their role in CM regeneration remain unclear. Here, we identified the long noncoding RNA Snhg1 as a driver to induce stable CM division and improve cardiac function after myocardial infarction (MI) by forming a positive feedback loop to sustain PI3K-Akt signaling activation. This finding might provide a novel therapeutic of Snhg1 as a promising regenerative approach to improve the prognosis of patients with heart failure.

developmental biology↗