Review
Biochemistry & Molecular Biology
Fuwen Yuan, William Hankey, Eric J. Wagner, Wei Li, Qianben Wang
Summary: Alternative polyadenylation (APA) is a molecular process that generates diversity at the 3' end of RNA polymerase II transcripts from over 60% of human genes, mainly occurring within the untranslated region (3'UTR), leading to significant impact on the regulatory potential of mRNA.
Article
Cell Biology
Shi-lu Chen, Zhong-xu Zhu, Xia Yang, Li-li Liu, Yang-fan He, Ming-ming Yang, Xin-yuan Guan, Xin Wang, Jing-ping Yun
Summary: APA plays a crucial role in HCC, with CPSF1 identified as a key regulator contributing to unfavorable survival outcomes in HCC. Knockdown of CPSF1 inhibits HCC cell proliferation and migration, while overexpression has the opposite effect. Knockdown of CPSF1 not only induces APA but also increases AS events.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Plant Sciences
Hui Ma, Juncheng Lin, Fangming Mei, Hude Mao, Qingshun Q. Li
Summary: The expression of homoeologous genes in allohexaploid wheat genome remains largely unknown at the co-transcriptional level. This study focused on alternative polyadenylation (APA) and found that drought stress led to extensive APA in wheat, involving a large number of stress-responsive genes. The study also revealed different poly(A) sites, APA patterns, and 3' UTR length changes among homoeologous genes. These findings shed light on the role of APA in drought stress response and provide new insights into the adaptability of homoeologous genes through transcriptome diversity.
Article
Biochemistry & Molecular Biology
Jesus Hernandez-Monge, Mayra Martinez-Sanchez, Adriana Rousset-Roman, Ixaura Medina-Medina, Vanesa Olivares-Illana
Summary: MDM2 regulates cell cycle progression by controlling the synthesis and degradation of RB protein in a cell cycle-specific manner. Under genotoxic stress, MDM2 enhances translation of RB mRNA to induce G1 cell cycle arrest, but ubiquitinates and degrades RB protein in the G2/M phase. The ATM phosphomimetic mutant MDM2(S395D) further confirms that MDM2's effect on RB levels is dependent on DNA damage.
Review
Microbiology
Rachael E. Turner, Traude H. Beilharz
Summary: Alternative polyadenylation (APA) plays a crucial role in regulating isoform-specific translation efficiency, stability, and localization. Despite advances in understanding APA in metazoans, its impact in Saccharomyces cerevisiae remains unclear. Experimental techniques are provided to uncover the functional importance of 3' UTR isoforms on translation, bridging the gap between observed APA and functional consequences.
Article
Biotechnology & Applied Microbiology
Chao Yan, Yupeng Wang, Tao Lyu, Zhikang Hu, Ning Ye, Weixin Liu, Jiyuan Li, Xiaohua Yao, Hengfu Yin
Summary: This study investigated genome-wide changes of polyadenylation sites under heat and cold stresses in Populus trichocarpa, revealing a comprehensive pattern of polyadenylation responsive to temperature stresses in trees. The results suggest that frequent changes in polyA tails may serve as a mechanism of gene regulation in response to stress, associated with distinct sequence signatures.
Article
Multidisciplinary Sciences
Junliang Wang, Wei Chen, Wenjun Yue, Wenhong Hou, Feng Rao, Hanbing Zhong, Yuanming Qi, Ni Hong, Ting Ni, Wenfei Jin
Summary: This study developed a single-cell polyadenylation sequencing method to investigate the landscape of alternative polyadenylation (APA) at the single-cell level. The results showed that genes with multiple polyA sites in bulk data tend to use only one site in each single cell. Cell cycle genes were found to have high variation in polyA site usages. Furthermore, polyA site usage switch played an important role in cell cycle regulation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Lorenzo Gallicchio, Gonzalo H. Olivares, Cameron W. Berry, Margaret T. Fuller
Summary: Alternative cleavage and polyadenylation (APA) is a co-transcriptional RNA processing process that greatly affects gene expression. APA occurs naturally during development and cellular differentiation, and changes in APA are associated with pathological states. The understanding of APA regulation and its impact on gene expression is still incomplete.
Article
Genetics & Heredity
Leonard Scharfen, Dagmar Zigackova, Kirsten A. Reimer, Martha R. Stark, Viktor A. Slat, Nancy J. Francoeur, Melissa L. Wells, Lecong Zhou, Perry J. Blackshear, Karla M. Neugebauer, Stephen D. Rader
Summary: By studying a highly diverged red alga, researchers discovered the presence of alternative polyadenylation (APA) in this non-model organism, suggesting its potential importance in regulating gene expression.
FRONTIERS IN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Yongtao Yu, Yuxiang Liufu, Yi Ren, Jie Zhang, Maoying Li, Shouwei Tian, Jinfang Wang, Shengjin Liao, Guoyi Gong, Haiying Zhang, Shaogui Guo
Summary: This study used PacBio single-molecule long-read sequencing to identify alternative splicing (AS), alternative polyadenylation (APA) and long non-coding RNAs (lncRNAs) in watermelon fruit. The results showed that these post-transcriptional mechanisms play important roles in fruit ripening, particularly the splicing isoforms associated with fruit ripening. Additionally, KEGG analysis revealed that fructose and mannose metabolism, starch and sucrose metabolism, and carotenoid biosynthesis were enriched in genes undergoing AS and APA.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Yanbo Yang, Xiaohong Wu, Wenqian Yang, Weiwei Jin, Dongyang Wang, Jianye Yang, Guanghui Jiang, Wen Zhang, Xiaohui Niu, Jing Gong
Summary: This study systematically characterized the alternative polyadenylation (APA) profiles during the differentiation of induced pluripotent stem cells (iPSCs) to cardiomyocytes. Five dynamic APA patterns were identified, with progressive lengthening of the 30UTR being the main pattern over time. The genes associated with this pattern were enriched in cell cycle and mRNA metabolic process pathways. TIA1 was indicated to play an important role in regulating APA events with this pattern. Additionally, APA and polyA machinery activity at the early differentiation stage could respond to developmental signal-mediated stimuli and result in a sharp shortening of the 30UTR. Furthermore, a miRNA-APA network was constructed, and several hub miRNAs potentially regulating cardiomyocyte differentiation were identified.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Review
Biochemistry & Molecular Biology
Jing Wu, Ligeng Ma, Ying Cao
Summary: Precursor message RNA needs processing to produce mature RNA. Cleavage and polyadenylation at the 3'-end in mRNA maturation is a crucial step. The poly(A) tail of mRNA is essential for nuclear export, stability, translation efficiency, and subcellular localization. Most genes have multiple mRNA isoforms through alternative splicing (AS) or alternative polyadenylation (APA), increasing transcriptome and proteome diversity. This review highlights recent advances in APA regulation of gene expression and stress responses in plants, suggesting APA as a novel strategy for plant adaptation to environmental changes and stress responses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Yizhe Sun, Dan Lu, Yue Yin, Jia Song, Yang Liu, Wenyan Hao, Fang Qi, Guangze Zhang, Xin Zhang, Liang Liu, Zhiqiang Lin, Hui Liang, Xuyang Zhao, Yan Jin, Yuxin Yin
Summary: PTEN is frequently mutated in human cancers and PTEN alpha, an isoform of PTEN, remains active in cancer bearing stop-gained PTEN mutations. Through counteraction of CD8(+) T cell-mediated cytotoxicity, PTEN alpha promotes T cell dysfunction and accelerates immune-resistant cancer progression. This suggests that PTEN alpha may be a potential target in antitumor immunotherapy.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Xiao-Mei Yu, Shu-Jun Li, Zi-Ting Yao, Jiao-Jiao Xu, Can-Can Zheng, Zhi-Chao Liu, Peng-Bo Ding, Zhi-Li Jiang, Xian Wei, Lin-Ping Zhao, Xing-Yuan Shi, Zhi-Gang Li, Wen Wen Xu, Bin Li
Summary: This study reveals that NAT10 mediates ac4C modification of lncRNA CTC-490G23.2, which enhances the stability and expression of lncRNA in ESCC and promotes tumor invasion and metastasis. Mechanistically, CTC-490G23.2 acts as a scaffold to increase the interaction between CD44 pre-mRNA and PTBP1, leading to an oncogenic splicing switch and increased stability of vimentin. The expression levels of CTC-490G23.2 and CD44v(8-10) can predict the prognosis of cancer patients.
Article
Biology
Yaoyu Jiao, Subba Reddy Palli
Summary: This study reveals the significant role of mitochondria in regulating insect wing growth during metamorphosis. By controlling mitochondrial activity, the development of insect wings is targeted. The findings provide insights into a novel molecular mechanism underlying developmental plasticity.
COMMUNICATIONS BIOLOGY
(2022)
Review
Surgery
Navamayooran Thavanesan, Sophie White, Shiela Lee, Bathiya Ratnayake, Kofi W. Oppong, Manu K. Nayar, Linda Sharp, Asbjorn Mohr Drewes, Gabriele Capurso, Enrique De-Madaria, Ajith K. Siriwardena, John A. Windsor, Sanjay Pandanaboyana
Summary: This article presents a systematic review and meta-analysis comparing the efficacy of different analgesic modalities in acute pancreatitis (AP). The results suggest that epidural analgesia is most effective within the first 24 hours, while NSAIDs can be an effective alternative to opiates during the first day.
WORLD JOURNAL OF SURGERY
(2022)
Article
Medicine, General & Internal
Klementina Ocskay, Mark Felix Juhasz, Nelli Farkas, Noemi Zadori, Lajos Szako, Zsolt Szakacs, Andrea Szentesi, Balint Eross, Emoke Miklos, Antal Zemplenyi, Bela Birkas, Arpad Csatho, Istvan Hartung, Tamas Nagy, Laszlo Czopf, Ferenc Izbeki, Laszlo Gajdan, Maria Papp, Laszlo Czako, Dora Illes, Marco Marino, Antonello Mirabella, Ewa Malecka-Panas, Hubert Zatorski, Yaroslav Susak, Kristina Opalchuk, Gabriele Capurso, Laura Apadula, Cristian Gheorghe, Ionut Adrian Saizu, Ole H. Petersen, Enrique De-Madaria, Jonas Rosendahl, Andrea Parniczky, Peter Hegyi
Summary: The REAPPEAR study aims to investigate whether a combined patient education and cessation programme for smoking and alcohol prevents acute recurrent pancreatitis (ARP) due to alcohol and/or tobacco abuse. The study consists of a randomised controlled trial and a prospective cohort study. Participants will receive standard intervention and laboratory testing, and interventions based on laboratory results. The primary endpoint is the 2-year all-cause recurrence rate of ARP and/or all-cause mortality.
Article
Microbiology
Cecilia Binda, Giulia Gibiino, Chiara Coluccio, Monica Sbrancia, Elton Dajti, Emanuele Sinagra, Gabriele Capurso, Vittorio Sambri, Alessandro Cucchetti, Giorgio Ercolani, Carlo Fabbri
Summary: The relationship between microbiota and biliary diseases is crucial for understanding the pathogenesis and developing effective treatments. However, more research is needed to fill the gaps in the current evidence.
Review
Medicine, General & Internal
Marco Lanzillotta, Matteo Tacelli, Massimo Falconi, Paolo Giorgio Arcidiacono, Gabriele Capurso, Emanuel Della-Torre
Summary: This systematic review and meta-analysis assessed the prevalence of endocrine and exocrine insufficiency in patients with autoimmune pancreatitis (AIP) and the impact of glucocorticoid (GC) therapy on pancreatic function. The study found that a large proportion of AIP patients displayed both endocrine and exocrine insufficiency at diagnosis. Long-term use of GCs was associated with an increased incidence of diabetes.
EUROPEAN JOURNAL OF INTERNAL MEDICINE
(2022)
Article
Endocrinology & Metabolism
Manuel Gentiluomo, Gabriele Capurso, Luca Morelli, Stefano Ermini, Claudio Pasquali, Anna Latiano, Francesca Tavano, William Greenhalf, Anna Caterina Milanetto, Stefano Landi, Susanne Roth, Ewa Malecka-Wojciesko, Eithne Costello, Krzysztof Jamroziak, Francesco Perri, Ugo Boggi, Daniela Basso, Fabio Farinati, Rudolf Kaaks, Giuseppe Vanella, Anna-Lea J. Gais Zurcher, Livia Archibugi, Rita T. Lawlor, Federico Canzian, Daniele Campa
Summary: This study generated a teloscore using 11 SNPs and found an association between genetically determined long telomeres and an increased risk of developing PanNEN. Two novel SNPs associated with PanNEN risk were also identified in this study.
NEUROENDOCRINOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Veronica Verdile, Francesca Svetoni, Piergiorgio La Rosa, Gabriele Ferrante, Eleonora Cesari, Claudio Sette, Maria Paola Paronetto
Summary: Alternative splicing is a crucial regulatory process for amplifying genomic information and expanding proteomic diversity, particularly in the brain. This study identifies the Ewing sarcoma protein (EWS) as a novel player in alternative splicing regulation during neuronal differentiation. EWS depletion in neuronal progenitor cells leads to premature differentiation and global changes in splicing regulation. EWS controls the alternative splicing of various genes, including the pivotal transcription factor FOXP1, contributing to the switch of gene expression underlying neuronal differentiation.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Gastroenterology & Hepatology
Florence E. M. de Rijk, Charlotte L. van Veldhuisen, Marc G. Besselink, Jeanin E. van Hooft, Hjalmar C. van Santvoort, Erwin J. M. van Geenen, Peter Hegyi, J-Matthias Lohr, Juan E. Dominguez-Munoz, Pieter Jan F. de Jonge, Marco J. Bruno, Robert C. Verdonk
Summary: A lack of consensus and substantial practice variation among international pancreatologists regarding the management of exocrine pancreatic insufficiency was identified in this study, emphasizing the need for further adaptation of guidelines based on current expert opinion and scientific evidence.
Review
Gastroenterology & Hepatology
Giuseppe Vanella, Domenico Tamburrino, Gabriele Capurso, Michiel Bronswijk, Michele Reni, Giuseppe Dell'Anna, Stefano Crippa, Schalk Van der Merwe, Massimo Falconi, Paolo Giorgio Arcidiacono
Summary: Upfront resection is less common for pancreatic ductal adenocarcinoma, and neoadjuvant treatments are increasingly used. However, complications such as jaundice, gastric outlet obstruction, and acute cholecystitis can lead to chemotherapy discontinuation, making effective management of these complications crucial. t-EUS has a high efficacy-invasiveness ratio compared to other methods, making it a powerful tool against chemotherapy discontinuation and potentially increasing subsequent resectability. Restricting t-EUS in potential surgical candidates is unsupported by evidence.
WORLD JOURNAL OF GASTROENTEROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Cinzia Caggiano, Marco Pieraccioli, Consuelo Pitolli, Gabriele Babini, Dinghai Zheng, Bin Tian, Pamela Bielli, Claudio Sette
Summary: This study uncovers a new role for androgen receptor (AR) in alternative cleavage and polyadenylation (APA) in prostate cancer. AR inhibition affects the rearrangement of APA subcomplexes and regulates transcriptome reprogramming. These findings are important for understanding the adaptive response of prostate cancer cells to hormonal therapy.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Marco Pieraccioli, Cinzia Caggiano, Luca Mignini, Chuwei Zhong, Gabriele Babini, Rossano Lattanzio, Savino Di Stasi, Bin Tian, Claudio Sette, Pamela Bielli
Summary: The selection of polyadenylation signals and alternative polyadenylation (APA) play important roles in gene expression regulation. This study uncovers a mechanism of APA regulation involving the interaction between XRN2 exonuclease and Sam68 RNA-binding protein. The increased expression of Sam68 in prostate cancer, promoted by MYC, leads to the usage of suboptimal proximal polyadenylation signals and enhances cell cycle-related gene translation. This finding suggests that the Sam68/XRN2-driven APA program may be a potential target for therapeutic strategies.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Valentina Panzeri, Marco Pieraccioli, Eleonora Cesari, Pierre de la Grange, Claudio Sette
Summary: Transcription-associated cyclin-dependent kinases (CDKs) regulate the transcription cycle through phosphorylation of RNA polymerase II (RNAPII). This study found that inhibiting CDK12 and CDK13 impaired splicing of specific promoter-proximal introns. The inhibition of CDK12/13 disrupted the interaction between SF3B1 and RNAPII, resulting in retention of these introns and a synergistic effect with another inhibitor on cell survival and cancer progression.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Psychiatry
Marika Guerra, Vanessa Medici, Robert Weatheritt, Valentina Corvino, Daniela Palacios, Maria Concetta Geloso, Donatella Farini, Claudio Sette
Summary: Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental syndrome characterized by social and communication impairment, repetitive behavior, and intellectual disability. Despite the association of multiple genes with ASD, most patients do not have detectable genetic alterations, suggesting the involvement of environmental factors. Transcriptome analysis reveals distinct gene expression patterns in autistic brains, providing insight into the mechanisms underlying the effects of genetic and environmental factors. A study focusing on the cerebellum, a brain area strongly associated with ASD, identifies a coordinated and temporally regulated gene expression program during postnatal development, enriched in ASD-linked genes. Dysregulation of these genes in the developing cerebellum of an ASD mouse model correlates with impaired social behavior and altered cerebellar morphology. The findings highlight the importance of understanding the complex transcriptional program related to ASD in cerebellar development and the dysregulation of genes in this brain area.
TRANSLATIONAL PSYCHIATRY
(2023)
Article
Oncology
Sabrina Gloria Giulia Testoni, Claudia Minici, Elisa Benetti, Francesca Clemente, Daniela Boselli, Clara Sciorati, Lucia De Monte, Maria Chiara Petrone, Markus Enderle, Walter Linzenbold, Maria Pia Protti, Angelo Manfredi, Francesco De Cobelli, Michele Reni, Massimo Falconi, Gabriele Capurso, Paolo Giorgio Arcidiacono, Emanuel Della-Torre
Summary: Thermal ablation under endoscopic ultrasound (EUS)-guidance has shown potential to enhance immune response in pancreatic ductal adenocarcinoma (PDAC). In a recent trial, EUS-guided ablation with HybridTherm Probe (HTP) in combination with chemotherapy improved disease progression compared to chemotherapy alone. This study explored the effects of EUS-HTP on systemic immune response in PDAC and found that it selectively affected immunological predictors of poor outcome.
Article
Biochemistry & Molecular Biology
Lidia Chellini, Marzia Scarfo, Davide Bonvissuto, Claudio Sette, Maria Paola Paronetto
Summary: In this study, researchers found that the DHX9/KDM2B complex can serve as a new drug target for treating aggressive Ewing sarcoma. By regulating the expression of the Hippo pathway regulator YAP1, this complex can influence the oncogenic properties of Ewing sarcoma cells.