{"title":"Coupling of alternative splicing and alternative polyadenylation.","authors":"Xueying Zhang, Feiyan Liu, Yu Zhou","doi":"10.3724/abbs.2024211","DOIUrl":"10.3724/abbs.2024211","url":null,"abstract":"<p><p>RNA splicing and 3'-cleavage and polyadenylation (CPA) are essential processes for the maturation of RNA. There have been extensive independent studies of these regulated processing events, including alternative splicing (AS) and alternative polyadenylation (APA). However, growing evidence suggests potential crosstalk between splicing and 3'-end processing in regulating AS or APA. Here, we first provide a brief overview of the molecular machines involved in splicing and 3'-end processing events, and then review recent studies on the functions and mechanisms of the crosstalk between the two processes. On the one hand, 3'-end processing can affect splicing, as 3'-end processing factors and CPA-generated polyA tail promote the splicing of the last intron. Beyond that, 3'-end processing factors can also influence the splicing of internal and terminal exons. Those 3'-end processing factors can also interact with different RNA-binding proteins (RBPs) to exert their effects on AS. The length of 3' untranslated region (3' UTR) can affect the splicing of upstream exons. On the other hand, splicing and CPA may compete within introns in generating different products. Furthermore, splicing within the 3' UTR is a significant factor contributing to 3' UTR diversity. Splicing also influences 3'-end processing through the actions of certain splicing factors. Interestingly, some classical RBPs play dual roles in both splicing and 3'-end processing. Finally, we discuss how long-read sequencing technologies aid in understanding the coordination of AS-APA events and envision that these findings may potentially promote the development of new strategies for disease diagnosis and treatment.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":"22-32"},"PeriodicalIF":3.3,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11802343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142778997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Multiple allostery in the regulation of PDGFR beta kinase activities.","authors":"Yanfeng Zhang, Meimei Wang, Guangcan Shao, Qingbin Shang, Mengqiu Dong, Xiaohong Qin, Li-Zhi Mi","doi":"10.3724/abbs.2024205","DOIUrl":"https://doi.org/10.3724/abbs.2024205","url":null,"abstract":"<p><p>Platelet-derived growth factor receptor beta (PDGFRβ), a type III receptor tyrosine kinase (RTK) with a featured kinase insert, regulates important cellular functions. Dysregulation of PDGFRβ is associated with cardiovascular and fibrosis diseases. Thus, its kinase activity needs to be precisely regulated under physiological conditions. Early studies demonstrated that its kinase is autoinhibited by its juxtamembrane segment and activated by transphosphorylation. However, additional mechanisms are required for the comprehensive regulation of the receptor kinase. Herein, we provide evidence that dimerization of activated kinases, autoinhibition by the kinase insert, and dimerization of inactive kinase, all contribute to the regulation of the receptor kinase. Moreover, we find such multiple allosteric regulation is also conserved in other type III RTKs, including colony stimulating factor 1 receptor (CSF1R). Impaired allosteric regulation of CSF1R is associated with malfunctions of microglia and demyelination of neurons in hereditary diffuse leukoencephalopathy with spheroids (HDLS).</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qingqing Xu, Yuxin Chen, Xinyan Ni, Hanying Zhuang, Shenxi Cao, Liwei Zhao, Leying Wang, Jianhui Chen, Wen Z Yang, Wenwen Zeng, Xi Li, Hongbin Sun, Wei L Shen
{"title":"High-resolution imaging atlas reveals the context-dependent role of pancreatic sympathetic innervation in diabetic mice.","authors":"Qingqing Xu, Yuxin Chen, Xinyan Ni, Hanying Zhuang, Shenxi Cao, Liwei Zhao, Leying Wang, Jianhui Chen, Wen Z Yang, Wenwen Zeng, Xi Li, Hongbin Sun, Wei L Shen","doi":"10.3724/abbs.2024215","DOIUrl":"https://doi.org/10.3724/abbs.2024215","url":null,"abstract":"<p><p>A better understanding of how sympathetic nerves impact pancreatic function is helpful for understanding diabetes. However, there is still uncertainty and controversy surrounding the roles of sympathetic nerves within the pancreas. To address this, we utilize high-resolution imaging and advanced three-dimensional (3D) reconstruction techniques to study the patterns of sympathetic innervation and morphology in the islets of adult wild-type (WT) and diabetic mice. Our data show that more than ~30% of α/β-cells are innervated by sympathetic nerves in both WT and diabetic mice. Additionally, sympathetic innervated α/β-cells are reduced in diet-induced obese (DIO) mice, whereas sympathetic innervated β-cells are increased in <i>db</i>/ <i>db</i> mice. In addition, <i>in situ</i> chemical pancreatic sympathetic denervation (cPSD) improves glucose tolerance in WT and <i>db</i>/ <i>db</i> mice but decreases glucose tolerance in DIO mice. <i>In situ</i> cPSD also enhances insulin sensitivity in diabetic mice without affecting WT mice. Overall, our findings advance our understanding of diabetes by highlighting the distinctive impact of pancreatic sympathetic innervation on glucose regulation.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Astatine-211 and actinium-225: two promising nuclides in targeted alpha therapy.","authors":"Dashan Zuo, Hui Wang, Boyi Yu, Qiang Li, Lu Gan, Weiqiang Chen","doi":"10.3724/abbs.2024206","DOIUrl":"https://doi.org/10.3724/abbs.2024206","url":null,"abstract":"<p><p>Nuclear medicine therapy offers a promising approach for tumor treatment, as the energy emitted during radionuclide decay causes irreparable damage to tumor cells. Notably, α-decay exhibits an even more significant destructive potential. By conjugating α-nuclides with antibodies or small-molecule inhibitors, targeted alpha therapy (TAT) can enhance tumor destruction while minimizing toxic side effects, making TAT an increasingly attractive antineoplastic strategy. Astatine-211 ( <sup>211</sup>At) and actinium-225 ( <sup>225</sup>Ac) have emerged as highly effective agents in TAT due to their exceptional physicochemical properties and biological effects. In this review, we highlight the applications of <sup>211</sup>At-/ <sup>225</sup>Ac-radiopharmaceuticals, particularly in specific tumor targets, such as prostate-specific membrane antigen (PSMA) in prostate cancers, cluster of differentiation (CD) in hematological malignancies, human epidermal growth factor receptor-2 (HER2) in ovarian cancers, and somatostatin receptor (SSTR) in neuroendocrine tumors. We synthesize the progress from preclinical and clinical trials to provide insights into the promising potential of <sup>211</sup>At-/ <sup>225</sup>Ac-radiopharmaceuticals for future treatments.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142714856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Huiyang Liu, Zhirong Chai, Ya Gao, Yanming Wang, Mengmeng Lu
{"title":"Ivermectin inhibits the growth of ESCC by activating the ATF4-mediated endoplasmic reticulum stress-autophagy pathway.","authors":"Huiyang Liu, Zhirong Chai, Ya Gao, Yanming Wang, Mengmeng Lu","doi":"10.3724/abbs.2024210","DOIUrl":"https://doi.org/10.3724/abbs.2024210","url":null,"abstract":"<p><p>Esophageal squamous cell carcinoma (ESCC) is one of the most common forms of malignancy worldwide. However, there is currently a lack of effective chemotherapeutic drugs for ESCC. Ivermectin is a broad-spectrum antiparasitic drug with notable antitumor activity. However, the cellular and molecular mechanisms by which ivermectin inhibits cancer growth remain unclear. In this study, we elucidate the role of ivermectin in ESCC suppression by activating the endoplasmic reticulum (ER) stress and autophagy pathways. In transcriptome analyses, we find that activating transcription factor 4 (ATF4) and DNA damage inducible transcript 3 (DDIT3) are involved in the activation of ER stress by ivermectin. Moreover, ivermectin treatment suppresses the growth of ESCC xenograft tumors in nude mice. Taken together, our results establish the antitumor molecular role of ivermectin in targeting the ER stress-autophagy pathway and suggest that ivermectin is a potential drug candidate for the treatment of ESCC.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"<i>Brucella</i> secretory protein VceA promotes FOXO1 entry into the nucleus to shift host cell metabolism toward glycolysis.","authors":"Shuzhu Cao, Xinxin Han, Xingmei Deng, Jia Guo, Liangbo Liu, Yu Zhang, Maratbek Suleimenov, Tianyi Zhao, Wei Li, Jian Ding, Songsong Xie, Hui Zhang","doi":"10.3724/abbs.2024203","DOIUrl":"https://doi.org/10.3724/abbs.2024203","url":null,"abstract":"<p><p>Increased glycolytic metabolism is a key step in the reproduction of <i>Brucella</i> and the induction of brucellosis, however, little is known about how this process is regulated during infection. Forkhead box protein O1 (FOXO1) is a transcription factor that regulates energy metabolism. In this study, we employ the yeast two-hybrid system (Y2H) and immunoprecipitation (Co-IP) to reverse screen for the FOXO1 for the first time and identify interactions between FOXO1 and the <i>Brucella</i> secretory protein VceA. Our findings reveal that the <i>Brucella</i> secretory protein VceA colocalizes with FOXO1 in the cytoplasm. Additionally, we observe that infection of macrophages with <i>Brucella abortus</i> <i>2308</i> ( <i>S2308</i>) promotes FOXO1 entry into the nucleus, leading to a significant upregulation of glycolysis level in macrophage. Conversely, in a VceA mutant strain (S2308-ΔVceA), we note a significant reduction in the ability of FOXO1 to enter the nucleus, accompanied by a decrease in glycolysis level. Furthermore, <i>Brucella</i> interacts with FOXO1 through the secreted protein VceA, promoting the entry of FOXO1 into the nucleus and thereby altering host metabolic patterns. This study provides insights into the mechanisms by which <i>Brucella</i> invades host macrophages and induces unique metabolic changes. These insights may offer a novel rationale for developing metabolic therapeutic strategies for the treatment and prevention of related diseases.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lei Zhang, Lina Yan, Xin Fu, Ziqi Tao, Shuna Liu, Rong Li, Ting Wang, Yepeng Mao, Wenwen Shang, Mi Gong, Xuemei Jia, Fang Wang
{"title":"PDK1 promotes epithelial ovarian cancer progression by upregulating BGN.","authors":"Lei Zhang, Lina Yan, Xin Fu, Ziqi Tao, Shuna Liu, Rong Li, Ting Wang, Yepeng Mao, Wenwen Shang, Mi Gong, Xuemei Jia, Fang Wang","doi":"10.3724/abbs.2024186","DOIUrl":"https://doi.org/10.3724/abbs.2024186","url":null,"abstract":"<p><p>Pyruvate dehydrogenase kinase 1 (PDK1) is a new therapeutic target that is dysregulated in multiple tumors. This study aims to explore the potential role and regulatory mechanism of PDK1 in epithelial ovarian cancer (EOC). We detect PDK1 expression in EOC tissues and cells using qRT-PCR and western blot analysis, and the effects of PDK1 on EOC cell malignant behaviors are explored. RNA sequencing analyses are performed to explore the differentially expressed genes in <i>PDK1</i>-silenced EOC cells. Furthermore, tumor-bearing mouse models are established to assess the impacts of PDK1 and BGN on EOC tumor growth and metastasis <i>in vivo</i>. The results show that PDK1 is upregulated in EOC tissues and cell lines. Biglycan (BGN) is downregulated in <i>PDK1</i>-silenced EOC cells, and its expression is positively correlated with PDK1 levels in EOC tissues. PDK1 depletion inhibits EOC cell proliferation, migration and invasion. Mechanistically, PDK1 and BGN are colocalized in the cytoplasm of EOC cells and interact with each other. PDK1 positively regulates BGN expression by enhancing <i>BGN</i> mRNA stability. BGN overexpression partially reverses the anti-tumor effects of PDK1 depletion on EOC cell malignant behaviors. PDK1 has also been revealed to upregulate BGN to activate the NF-κB oncogenic pathway in EOC cells. Additionally, PDK1 accelerates tumor growth and metastasis by modulating BGN expression. In conclusion, <i>PDK1</i> functions as an oncogene, facilitating EOC progression by upregulating BGN and activating the NF-κB pathway. These findings may provide valuable biomarkers for the diagnosis and treatment of EOC.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"RNA modifications: emerging players in the regulation of reproduction and development.","authors":"Junfei Wen, Qifan Zhu, Yong Liu, Lan-Tao Gou","doi":"10.3724/abbs.2024201","DOIUrl":"10.3724/abbs.2024201","url":null,"abstract":"<p><p>The intricate world of RNA modifications, collectively termed the epitranscriptome, covers over 170 identified modifications and impacts RNA metabolism and, consequently, almost all biological processes. In this review, we focus on the regulatory roles and biological functions of a panel of dominant RNA modifications (including m <sup>6</sup>A, m <sup>5</sup>C, Ψ, ac <sup>4</sup>C, m <sup>1</sup>A, and m <sup>7</sup>G) on three RNA types-mRNA, tRNA, and rRNA-in mammalian development, particularly in the context of reproduction as well as embryonic development. We discuss in detail how those modifications, along with their regulatory proteins, affect RNA processing, structure, localization, stability, and translation efficiency. We also highlight the associations among dysfunctions in RNA modification-related proteins, abnormal modification deposition and various diseases, emphasizing the roles of RNA modifications in critical developmental processes such as stem cell self-renewal and cell fate transition. Elucidating the molecular mechanisms by which RNA modifications influence diverse developmental processes holds promise for developing innovative strategies to manage developmental disorders. Finally, we outline several unexplored areas in the field of RNA modification that warrant further investigation.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":"33-58"},"PeriodicalIF":3.3,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11802351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}