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a b s t r a c tSGs are mRNA containing cytoplasmic structures that are assembled in response to stress. Tudor-SN protein is a ubiquitously expressed protein. Here, Tudor-SN protein was found to physiologically interact with G3BP, which is the marker and effector of SG. The kinetics of the assembly of SGs in the living cells demonstrated that Tudor-SN co-localizes with G3BP and is recruited to the same SGs in response to different stress stimuli. Knockdown of endogenous Tudor-SN did not inhibit the formation of SGs, but retarded the aggregation of small SGs into large SGs. Thus Tudor-SN may not be an initiator as essential as G3BP for the formation of SGs, but affects the aggregation of SGs. These findings identify Tudor-SN as a novel component of SGs. Structured summary:MINT-7968768, MINT-7968779: Tudor-SN (uniprotkb:Q7KZF4) physically interacts (MI:0915) with G3BP

Background: Human Tudor staphylococcal nuclease (Tudor-SN) is involved in the snRNP assembly. Results: The efficient formation of Tudor-SN⅐SmB complex requires binding orientation of the methylated ligand and the specific binding pocket. Conclusion: Tudor-SN takes part in regulating pre-mRNA splicing via the recruitment of U5 snRNP and the association of Sm protein.Significance: The mechanism underlying the involvement of Tudor-SN in regulating snRNP biogenesis was revealed.

Multifunctional SND1 (staphylococcal nuclease and tudor domain containing 1) protein is reportedly associated with different types of RNA molecules, including mRNA, miRNA, pre-miRNA, and dsRNA. SND1 has been implicated in a number of biological processes in eukaryotic cells, including cell cycle, DNA damage repair, proliferation, and apoptosis. However, the specific molecular mechanism regarding the anti-apoptotic role of SND1 in mammalian cells remains largely elusive. In this study, the analysis of the online HPA (human protein atlas) and TCGA (the cancer genome atlas) databases showed the significantly high expression of SND1 in liver cancer patients. We found that the downregulation or complete depletion of SND1 enhanced the apoptosis levels of HepG2 and SMMC-7721 cells upon stimulation with 5-Fu (5-fluorouracil), a chemotherapeutic drug for HCC (hepatocellular carcinoma). SND1 affected the 5-Fu-induced apoptosis levels of HCC cells by modulating the expression of UCA1 (urothelial cancer associated 1), which is a lncRNA (long non-coding RNA). Moreover, MYB (MYB proto-oncogene, transcription factor) may be involved in the regulation of SND1 in UCA1 expression. In summary, our study identified SND1 as an anti-apoptotic factor in hepatocellular carcinoma cells via the modulation of lncRNA UCA1, which sheds new light on the relationship between SND1 protein and lncRNA.

Stress granules (SGs) and processing bodies (PBs) comprise the main types of cytoplasmic RNA foci during stress. Our previous data indicate that knockdown of human Tudor staphylococcal nuclease (Tudor-SN) affects the aggregation of SGs. However, the precise molecular mechanism has not been determined fully. In the present study, we demonstrate that Tudor-SN binds and colocalizes with many core components of SGs, such as poly(A) + mRNA binding protein 1, T-cell internal antigen-1-related protein and poly(A) + mRNA, and SG/PB sharing proteins Argonaute 1/2, but not PB core proteins, such as decapping enzyme 1 a/b, confirming that Tudor-SN is an SG-specific protein. We also demonstrate that the Tudor-SN granule actively communicates with the nuclear and cytosolic pool under stress conditions. Tudor-SN can regulate the aggregation dynamics of poly(A) + mRNA-containing SGs and selectively stabilize the SG-associated mRNA during cellular stress.

Posttranslational modifications of certain stress granule (SG) proteins are closely related to the assembly of SGs, a type of cytoplasmic foci structure. Our previous studies revealed that the Tudor staphylococcal nuclease (Tudor-SN) protein participates in the formation of SGs. However, the functional significance of potential Tudor-SN modifications during stress has not been reported. In this study, we demonstrated that the Tudor-SN protein was phosphorylated at threonine 103 (T103) upon stimulation with arsenite. In addition, c-Jun N-terminal kinase (JNK) was found to be responsible for Tudor-SN phosphorylation at the T103 site. We further illustrated that either a T103A mutation or the suppression of phosphorylation of T103 by the JNK inhibitor SP600125 inhibited the efficient recruitment of Tudor-SN into SGs. In addition, the T103A mutation could affect the physical binding of Tudor-SN with the G3BP (Ras-GAP SH3 domain-binding protein) protein but not with the HuR (Hu antigen R) protein and AGTR1-3'UTR (3'-untranslated region of angiotensin II receptor, type 1) mRNA cargo. These data suggested that JNK-enhanced Tudor-SN phosphorylation promotes the interaction between Tudor-SN and G3BP and facilitates the efficient recruitment of Tudor-SN into SGs under conditions of sodium arsenite-induced oxidative stress. This finding provides novel insights into the physiological function of Tudor-SN modification.

Berberine (BBR) is a natural isoquinoline alkaloid, which is used in traditional medicine for its anti‐microbial, anti‐protozoal, anti‐diarrhoeal activities. Berberine interacts with DNA and displays anti‐cancer activities, yet its effects on cellular DNA repair and on synthetic treatments with chemotherapeutic drugs remain unclear. In this study, we investigated the effects of BBR on DNA repair and on sensitization of breast cancer cells to different types of DNA damage anti‐tumoural drugs. We found BBR arrested cells in the cell cycle S phase and induced DNA breaks. Cell growth analysis showed BBR sensitized MDA‐MB‐231 cells to cisplatin, camptothecin and methyl methanesulfonate; however, BBR had no synergistic effects with hydroxurea and olaparib. These results suggest BBR only affects specific DNA repair pathways. Western blot showed BBR down‐regulated XRCC1 expressions, and the rescued XRCC1 recovered the resistance of cancer cells to BBR. Therefore, we conclude that BBR interferes with XRCC1‐mediated base excision repair to sensitize cancer cells to chemotherapeutic drugs. These finding can contribute to understanding the effects of BBR on cellular DNA repair and the clinical employment of BBR in treatment of breast cancer.

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