No abstract

Histone ubiquitination regulates sperm formation and is important for nucleosome removal during spermatogenesis. RNF8 is an E3 ubiquitin ligase, and RAD6B is an E2 ubiquitin-conjugating enzyme. Both proteins participate in DNA damage repair processes via histone ubiquitination. Loss of RNF8 or RAD6B can lead to sterility in male mice. However, the specific mechanisms regulating these ubiquitin-mediated processes are unclear. In this study, we found that RNF8 knockout mice were either subfertile or sterile based on the numbers of offspring they produced. We explored the mechanism by which RAD6B and RNF8 knockouts cause infertility in male mice and compared the effects of their loss on spermatogenesis. Our results demonstrate that RAD6B can polyubiquitinate histones H2 A and H2B. In addition, RNF8 was shown to monoubiquitinate histones H2 A and H2B. Furthermore, we observed that absence of histone ubiquitination was not the only reason for infertility. Senescence played a role in intensifying male sterility by affecting the number of germ cells during spermatogenesis. In summary, both histone ubiquitination and senescence play important roles in spermatogenesis.

No abstract

Tumorigenesis is a complicated process caused by successive genetic and epigenetic alterations. The past decades demonstrated that the immune system affects tumorigenesis, tumor progression, and metastasis. Although increasing immunotherapies are revealed, only a tiny proportion of them are effective. Long non-coding RNAs (lncRNAs) are a class of single-stranded RNA molecules larger than 200 nucleotides and are essential in the molecular network of oncology and immunology. Increasing researches have focused on the connection between lncRNAs and cancer immunotherapy. However, the in-depth mechanisms are still elusive. In this review, we outline the latest studies on the functions of lncRNAs in the tumor immune microenvironment. Via participating in various biological processes such as neutrophil recruitment, macrophage polarization, NK cells cytotoxicity, and T cells functions, lncRNAs regulate tumorigenesis, tumor invasion, epithelial-mesenchymal transition (EMT), and angiogenesis. In addition, we reviewed the current understanding of the relevant strategies for targeting lncRNAs. LncRNAs-based therapeutics may represent promising approaches in serving as prognostic biomarkers or potential therapeutic targets in cancer, providing ideas for future research and clinical application on cancer diagnosis and therapies.

RAD6 participates in DNA double-strand breaks (DSBs) repair by ubiquitinating histone H2B in mitotic cells. In terminally differentiated cells, however, the mechanisms of DNA damage repair are less well known. In this study, we investigate whether RAD6B is involved in DSBs repair in neurons and effects of RAD6B deficiency on neuronal survival. We compared neurons of RAD6B-deficient mice with those of littermate wild type (WT) mice and induced DNA damage by X-ray irradiation. We provide evidence that RAD6B is essential for neural DDR and RAD6B deficiency results in increased genomic instability and neurodegeneration. Moreover, higher levels of p53 and p21 are present in the brains of RAD6B-deficient mice, which may be responsible for neuronal senescence, and degeneration. In addition, behavioral experiments show that RAD6B-deficient mice exhibit marked learning and memory deficits. In conclusion, these findings suggest that RAD6B is critical for neural integrity and that the absence of RAD6B accelerates neurodegeneration in mice.