Pub Date : 2023-07-01Epub Date: 2023-01-19DOI: 10.1002/wrna.1772
Valeria Lodde, Matteo Floris, Enrico Zoroddu, Ignazio Roberto Zarbo, Maria Laura Idda
Autoimmune diseases (ADs) are chronic pathologies generated by the loss of immune tolerance to the body's own cells and tissues. There is growing recognition that RNA-binding proteins (RBPs) critically govern immunity in healthy and pathological conditions by modulating gene expression post-transcriptionally at all levels: nuclear mRNA splicing and modification, export to the cytoplasm, as well as cytoplasmic mRNA transport, storage, editing, stability, and translation. Despite enormous efforts to identify new therapies for ADs, definitive solutions are not yet available in many instances. Recognizing that many ADs have a strong genetic component, we have explored connections between the molecular biology and the genetics of RBPs in ADs. Here, we review the genetics and molecular biology of RBPs in four major ADs, multiple sclerosis (MS), type 1 diabetes mellitus (T1D), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). We anticipate that gaining insights into the genetics and biology of ADs can facilitate the discovery of new therapies. This article is categorized under: RNA in Disease and Development > RNA in Disease.
{"title":"RNA-binding proteins in autoimmunity: From genetics to molecular biology.","authors":"Valeria Lodde, Matteo Floris, Enrico Zoroddu, Ignazio Roberto Zarbo, Maria Laura Idda","doi":"10.1002/wrna.1772","DOIUrl":"10.1002/wrna.1772","url":null,"abstract":"<p><p>Autoimmune diseases (ADs) are chronic pathologies generated by the loss of immune tolerance to the body's own cells and tissues. There is growing recognition that RNA-binding proteins (RBPs) critically govern immunity in healthy and pathological conditions by modulating gene expression post-transcriptionally at all levels: nuclear mRNA splicing and modification, export to the cytoplasm, as well as cytoplasmic mRNA transport, storage, editing, stability, and translation. Despite enormous efforts to identify new therapies for ADs, definitive solutions are not yet available in many instances. Recognizing that many ADs have a strong genetic component, we have explored connections between the molecular biology and the genetics of RBPs in ADs. Here, we review the genetics and molecular biology of RBPs in four major ADs, multiple sclerosis (MS), type 1 diabetes mellitus (T1D), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). We anticipate that gaining insights into the genetics and biology of ADs can facilitate the discovery of new therapies. This article is categorized under: RNA in Disease and Development > RNA in Disease.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9777685","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}
Pub Date : 2023-07-01Epub Date: 2023-01-02DOI: 10.1002/wrna.1774
Padmaja D Wakchaure, Bishwajit Ganguly
During the last decade, riboswitches emerged as new small-molecule sensing RNA in bacteria. Thiamine pyrophosphate (TPP) riboswitch is widely distributed and occurs in plants, bacteria, fungi, and archaea. Extensive biochemical, structural, and genetic studies have been carried out to elucidate the recognition mechanism of TPP riboswitches. However, a comprehensive report summarizing all information on recognition principles and newly designed ligands for TPP riboswitch is scarce in the literature. This review gives a comprehensive understanding of the TPP riboswitch's structure, mechanism, and methods applied to design ligands for the TPP riboswitch. The ligand-bound TPP riboswitch was studied with various experimental and theoretical techniques to elucidate the conformational dynamics. The mutation studies shed light on the significance of pyrimidine sensing helix for the binding of ligands. Further, the structure-activity relationship study and fragment-based approach lead to the development of ligands with Kd values at the sub-micromolar level. However, there is a need to design more potent inhibitors for TPP riboswitch for therapeutic applications. The recent advancements in ligand design highlight the TPP riboswitch as a promising target for developing new antibiotics. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Riboswitches Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs.
{"title":"Exploring the structure, function of thiamine pyrophosphate riboswitch, and designing small molecules for antibacterial activity.","authors":"Padmaja D Wakchaure, Bishwajit Ganguly","doi":"10.1002/wrna.1774","DOIUrl":"10.1002/wrna.1774","url":null,"abstract":"<p><p>During the last decade, riboswitches emerged as new small-molecule sensing RNA in bacteria. Thiamine pyrophosphate (TPP) riboswitch is widely distributed and occurs in plants, bacteria, fungi, and archaea. Extensive biochemical, structural, and genetic studies have been carried out to elucidate the recognition mechanism of TPP riboswitches. However, a comprehensive report summarizing all information on recognition principles and newly designed ligands for TPP riboswitch is scarce in the literature. This review gives a comprehensive understanding of the TPP riboswitch's structure, mechanism, and methods applied to design ligands for the TPP riboswitch. The ligand-bound TPP riboswitch was studied with various experimental and theoretical techniques to elucidate the conformational dynamics. The mutation studies shed light on the significance of pyrimidine sensing helix for the binding of ligands. Further, the structure-activity relationship study and fragment-based approach lead to the development of ligands with K<sub>d</sub> values at the sub-micromolar level. However, there is a need to design more potent inhibitors for TPP riboswitch for therapeutic applications. The recent advancements in ligand design highlight the TPP riboswitch as a promising target for developing new antibiotics. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Riboswitches Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9842096","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}
Pub Date : 2023-07-01Epub Date: 2023-01-06DOI: 10.1002/wrna.1771
Ryan P Kempen, Preeti Dabas, Aseem Z Ansari
The largest subunit of RNA polymerase II (Pol II) has an unusual carboxyl-terminal domain (CTD). This domain is composed of a tandemly repeating heptapeptide, Y1 S2 P3 T4 S5 P6 S7 , that has multiple roles in regulating Pol II function and processing newly synthesized RNA. Transient phosphorylation of Ser2 and Ser5 of the YS2 PTS5 PS repeat have well-defined roles in recruiting different protein complexes and coordinating sequential steps in gene transcription. As such, these phospho-marks encipher a molecular recognition code, colloquially termed the CTD code. In contrast, the contribution of phospho-Threonine 4 (pThr4/pT4) to the CTD code remains opaque and contentious. Fuelling the debate on the relevance of this mark to gene expression are the findings that replacing Thr4 with a valine or alanine has varied impact on cellular function in different species and independent proteomic analyses disagree on the relative abundance of pThr4 marks. Yet, substitution with negatively charged residues is lethal and even benign mutations selectively disrupt synthesis and 3' processing of distinct sets of coding and non-coding transcripts. Suggestive of non-canonical roles, pThr4 marked Pol II regulates distinct gene classes in a species- and signal-responsive manner. Hinting at undiscovered roles of this elusive mark, multiple signal-responsive kinases phosphorylate Thr4 at target genes. Here, we focus on this under-explored residue and postulate that the pThr4 mark is superimposed on the canonical CTD code to selectively regulate expression of targeted genes without perturbing genome-wide transcriptional processes. This article is categorized under: RNA Processing > 3' End Processing RNA Processing > Processing of Small RNAs RNA Processing > Splicing Regulation/Alternative Splicing.
{"title":"The Phantom Mark: Enigmatic roles of phospho-Threonine 4 modification of the C-terminal domain of RNA polymerase II.","authors":"Ryan P Kempen, Preeti Dabas, Aseem Z Ansari","doi":"10.1002/wrna.1771","DOIUrl":"10.1002/wrna.1771","url":null,"abstract":"<p><p>The largest subunit of RNA polymerase II (Pol II) has an unusual carboxyl-terminal domain (CTD). This domain is composed of a tandemly repeating heptapeptide, Y<sub>1</sub> S<sub>2</sub> P<sub>3</sub> T<sub>4</sub> S<sub>5</sub> P<sub>6</sub> S<sub>7</sub> , that has multiple roles in regulating Pol II function and processing newly synthesized RNA. Transient phosphorylation of Ser2 and Ser5 of the YS<sub>2</sub> PTS<sub>5</sub> PS repeat have well-defined roles in recruiting different protein complexes and coordinating sequential steps in gene transcription. As such, these phospho-marks encipher a molecular recognition code, colloquially termed the CTD code. In contrast, the contribution of phospho-Threonine 4 (pThr4/pT4) to the CTD code remains opaque and contentious. Fuelling the debate on the relevance of this mark to gene expression are the findings that replacing Thr4 with a valine or alanine has varied impact on cellular function in different species and independent proteomic analyses disagree on the relative abundance of pThr4 marks. Yet, substitution with negatively charged residues is lethal and even benign mutations selectively disrupt synthesis and 3' processing of distinct sets of coding and non-coding transcripts. Suggestive of non-canonical roles, pThr4 marked Pol II regulates distinct gene classes in a species- and signal-responsive manner. Hinting at undiscovered roles of this elusive mark, multiple signal-responsive kinases phosphorylate Thr4 at target genes. Here, we focus on this under-explored residue and postulate that the pThr4 mark is superimposed on the canonical CTD code to selectively regulate expression of targeted genes without perturbing genome-wide transcriptional processes. This article is categorized under: RNA Processing > 3' End Processing RNA Processing > Processing of Small RNAs RNA Processing > Splicing Regulation/Alternative Splicing.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10323045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9786436","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}
Pub Date : 2023-07-01Epub Date: 2023-01-11DOI: 10.1002/wrna.1775
Ping Sun, Mengjie Chen, Suren R Sooranna, Deshun Shi, Qingyou Liu, Hui Li
Many indicators can be used to evaluate the productivity and quality of livestock, such as meat and milk production as well as fat deposition. Meat and milk production are measures of livestock performance, while fat deposition affects the taste and flavor of the meat. The circRNAs, are non-coding RNAs, that are involved in the regulation of all these three traits. We review the functions and mechanisms of circRNAs in muscle and fat development as well as lactation to provide a theoretical basis for circRNA research in animal husbandry. Various phenotypic changes presented in livestock may be produced by different circRNAs. Our current concern is how to use the roles played by circRNAs to our advantage to produce the best possible livestock. Hence, we describe the advantages and disadvantages of knockout techniques for circRNAs. In addition, we also put forward our thoughts regarding the mechanism and network of circRNAs to provide researchers with novel ideas of how molecular biology can help us advance our goals in animal farming. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications RNA Interactions with Proteins and Other Molecules > Protein-RNA Recognition RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.
{"title":"The emerging roles of circRNAs in traits associated with livestock breeding.","authors":"Ping Sun, Mengjie Chen, Suren R Sooranna, Deshun Shi, Qingyou Liu, Hui Li","doi":"10.1002/wrna.1775","DOIUrl":"10.1002/wrna.1775","url":null,"abstract":"<p><p>Many indicators can be used to evaluate the productivity and quality of livestock, such as meat and milk production as well as fat deposition. Meat and milk production are measures of livestock performance, while fat deposition affects the taste and flavor of the meat. The circRNAs, are non-coding RNAs, that are involved in the regulation of all these three traits. We review the functions and mechanisms of circRNAs in muscle and fat development as well as lactation to provide a theoretical basis for circRNA research in animal husbandry. Various phenotypic changes presented in livestock may be produced by different circRNAs. Our current concern is how to use the roles played by circRNAs to our advantage to produce the best possible livestock. Hence, we describe the advantages and disadvantages of knockout techniques for circRNAs. In addition, we also put forward our thoughts regarding the mechanism and network of circRNAs to provide researchers with novel ideas of how molecular biology can help us advance our goals in animal farming. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications RNA Interactions with Proteins and Other Molecules > Protein-RNA Recognition RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9842114","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}
Hongyan Chen, Xiaoting Zhang, Hao Su, Judeng Zeng, Hung Chan, Qing Li, Xiaodong Liu, Lin Zhang, William Ka Kei Wu, Matthew Tak Vai Chan, Huarong Chen
Sepsis is defined as life-threatening organ dysfunction caused by the host immune dysregulation to infection. It is a highly heterogeneous syndrome with complex pathophysiological mechanisms. The host immune response to sepsis can be divided into hyper-inflammatory and immune-suppressive phases which could exist simultaneously. In the initial stage, systemic immune response is activated after exposure to pathogens. Both innate and adaptive immune cells undergo epigenomic, transcriptomic, and functional reprogramming, resulting in systemic and persistent inflammatory responses. Following the hyper-inflammatory phase, the body is in a state of continuous immunosuppression, which is related to immune cell apoptosis, metabolic failure, and epigenetic reprogramming. Immunosuppression leads to increased susceptibility to secondary infections in patients with sepsis. RNA N6-Methyladenosine (m6A) has been recognized as an indispensable epitranscriptomic modification involved in both physiological and pathological processes. Recent studies suggest that m6A could reprogram both innate and adaptive immune cells through posttranscriptional regulation of RNA metabolism. Dysregulated m6A modifications contribute to the pathogenesis of immune-related diseases. In this review, we summarize immune cell changes and the potential role of m6A modification in sepsis. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Processing > RNA Editing and Modification.
{"title":"Immune dysregulation and RNA N6-methyladenosine modification in sepsis.","authors":"Hongyan Chen, Xiaoting Zhang, Hao Su, Judeng Zeng, Hung Chan, Qing Li, Xiaodong Liu, Lin Zhang, William Ka Kei Wu, Matthew Tak Vai Chan, Huarong Chen","doi":"10.1002/wrna.1764","DOIUrl":"https://doi.org/10.1002/wrna.1764","url":null,"abstract":"<p><p>Sepsis is defined as life-threatening organ dysfunction caused by the host immune dysregulation to infection. It is a highly heterogeneous syndrome with complex pathophysiological mechanisms. The host immune response to sepsis can be divided into hyper-inflammatory and immune-suppressive phases which could exist simultaneously. In the initial stage, systemic immune response is activated after exposure to pathogens. Both innate and adaptive immune cells undergo epigenomic, transcriptomic, and functional reprogramming, resulting in systemic and persistent inflammatory responses. Following the hyper-inflammatory phase, the body is in a state of continuous immunosuppression, which is related to immune cell apoptosis, metabolic failure, and epigenetic reprogramming. Immunosuppression leads to increased susceptibility to secondary infections in patients with sepsis. RNA N6-Methyladenosine (m6A) has been recognized as an indispensable epitranscriptomic modification involved in both physiological and pathological processes. Recent studies suggest that m6A could reprogram both innate and adaptive immune cells through posttranscriptional regulation of RNA metabolism. Dysregulated m6A modifications contribute to the pathogenesis of immune-related diseases. In this review, we summarize immune cell changes and the potential role of m6A modification in sepsis. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Processing > RNA Editing and Modification.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10035870","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}
Antonio J Montero-Hidalgo, Jesús M Pérez-Gómez, Antonio J Martínez-Fuentes, Enrique Gómez-Gómez, Manuel D Gahete, Juan M Jiménez-Vacas, Raúl M Luque
Bladder cancer is the most common malignancy of the urinary tract worldwide. The therapeutic options to tackle this disease comprise surgery, intravesical or systemic chemotherapy, and immunotherapy. Unfortunately, a wide number of patients ultimately become resistant to these treatments and develop aggressive metastatic disease, presenting a poor prognosis. Therefore, the identification of novel therapeutic approaches to tackle this devastating pathology is urgently needed. However, a significant limitation is that the progression and drug response of bladder cancer is strongly associated with its intrinsic molecular heterogeneity. In this sense, RNA splicing is recently gaining importance as a critical hallmark of cancer since can have a significant clinical value. In fact, a profound dysregulation of the splicing process has been reported in bladder cancer, especially in the expression of certain key splicing variants and circular RNAs with a potential clinical value as diagnostic/prognostic biomarkers or therapeutic targets in this pathology. Indeed, some authors have already evidenced a profound antitumor effect by targeting some splicing factors (e.g., PTBP1), mRNA splicing variants (e.g., PKM2, HYAL4‐v1), and circular RNAs (e.g., circITCH, circMYLK), which illustrates new possibilities to significantly improve the management of this pathology. This review represents the first detailed overview of the splicing process and its alterations in bladder cancer, and highlights opportunities for the development of novel diagnostic/prognostic biomarkers and their clinical potential for the treatment of this devastating cancer type.
{"title":"Alternative splicing in bladder cancer: potential strategies for cancer diagnosis, prognosis, and treatment.","authors":"Antonio J Montero-Hidalgo, Jesús M Pérez-Gómez, Antonio J Martínez-Fuentes, Enrique Gómez-Gómez, Manuel D Gahete, Juan M Jiménez-Vacas, Raúl M Luque","doi":"10.1002/wrna.1760","DOIUrl":"https://doi.org/10.1002/wrna.1760","url":null,"abstract":"Bladder cancer is the most common malignancy of the urinary tract worldwide. The therapeutic options to tackle this disease comprise surgery, intravesical or systemic chemotherapy, and immunotherapy. Unfortunately, a wide number of patients ultimately become resistant to these treatments and develop aggressive metastatic disease, presenting a poor prognosis. Therefore, the identification of novel therapeutic approaches to tackle this devastating pathology is urgently needed. However, a significant limitation is that the progression and drug response of bladder cancer is strongly associated with its intrinsic molecular heterogeneity. In this sense, RNA splicing is recently gaining importance as a critical hallmark of cancer since can have a significant clinical value. In fact, a profound dysregulation of the splicing process has been reported in bladder cancer, especially in the expression of certain key splicing variants and circular RNAs with a potential clinical value as diagnostic/prognostic biomarkers or therapeutic targets in this pathology. Indeed, some authors have already evidenced a profound antitumor effect by targeting some splicing factors (e.g., PTBP1), mRNA splicing variants (e.g., PKM2, HYAL4‐v1), and circular RNAs (e.g., circITCH, circMYLK), which illustrates new possibilities to significantly improve the management of this pathology. This review represents the first detailed overview of the splicing process and its alterations in bladder cancer, and highlights opportunities for the development of novel diagnostic/prognostic biomarkers and their clinical potential for the treatment of this devastating cancer type.","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9675575","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}
Pub Date : 2023-05-01Epub Date: 2022-08-12DOI: 10.1002/wrna.1754
Jaikrishna Balakittnen, Chameera Ekanayake Weeramange, Daniel F Wallace, Pascal H G Duijf, Alexandre S Cristino, Liz Kenny, Sarju Vasani, Chamindie Punyadeera
Oral cancer (OC) is the most prevalent subtype of cancer arising in the head and neck region. OC risk is mainly attributed to behavioral risk factors such as exposure to tobacco and excessive alcohol consumption, and a lesser extent to viral infections such as human papillomaviruses and Epstein-Barr viruses. In addition to these acquired risk factors, heritable genetic factors have shown to be associated with OC risk. Despite the high incidence, biomarkers for OC diagnosis are lacking and consequently, patients are often diagnosed in advanced stages. This delay in diagnosis is reflected by poor overall outcomes of OC patients, where 5-year overall survival is around 50%. Among the biomarkers proposed for cancer detection, noncoding RNA (ncRNA) can be considered as one of the most promising categories of biomarkers due to their role in virtually all cellular processes. Similar to other cancer types, changes in expressions of ncRNAs have been reported in OC and a number of ncRNAs have diagnostic, prognostic, and therapeutic potential. Moreover, some ncRNAs are capable of regulating gene expression by various mechanisms. Therefore, elucidating the current literature on the four main types of ncRNAs namely, microRNA, lncRNA, snoRNA, piwi-RNA, and circular RNA in the context of OC pathogenesis is timely and would enable further improvements and innovations in diagnosis, prognosis, and treatment of OC. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA in Disease and Development > RNA in Development.
口腔癌(OC)是头颈部最常见的癌症亚型。口腔癌风险主要归因于行为风险因素,如吸烟和过度饮酒,其次是病毒感染,如人类乳头状瘤病毒和爱泼斯坦-巴氏病毒。除了这些获得性风险因素外,遗传因素也与卵巢癌风险有关。尽管卵巢癌的发病率很高,但目前还缺乏诊断卵巢癌的生物标志物,因此患者往往在晚期才被诊断出来。OC患者的总体预后较差,5年总生存率约为50%,这反映了诊断的延误。在建议用于癌症检测的生物标记物中,非编码 RNA(ncRNA)可被视为最有前景的生物标记物类别之一,因为它们在几乎所有细胞过程中都发挥作用。与其他癌症类型类似,有报道称非编码 RNA 在肿瘤细胞中的表达也发生了变化,而且一些非编码 RNA 具有诊断、预后和治疗的潜力。此外,一些 ncRNA 还能通过各种机制调节基因表达。因此,阐明目前关于四种主要 ncRNA(即 microRNA、lncRNA、snoRNA、piwi-RNA 和 circular RNA)在 OC 发病机制中的作用的文献十分及时,这将有助于进一步改进和创新 OC 的诊断、预后和治疗。本文归类于RNA in Disease and Development > RNA in Disease RNA in Disease and Development > RNA in Development。
{"title":"Noncoding RNAs in oral cancer.","authors":"Jaikrishna Balakittnen, Chameera Ekanayake Weeramange, Daniel F Wallace, Pascal H G Duijf, Alexandre S Cristino, Liz Kenny, Sarju Vasani, Chamindie Punyadeera","doi":"10.1002/wrna.1754","DOIUrl":"10.1002/wrna.1754","url":null,"abstract":"<p><p>Oral cancer (OC) is the most prevalent subtype of cancer arising in the head and neck region. OC risk is mainly attributed to behavioral risk factors such as exposure to tobacco and excessive alcohol consumption, and a lesser extent to viral infections such as human papillomaviruses and Epstein-Barr viruses. In addition to these acquired risk factors, heritable genetic factors have shown to be associated with OC risk. Despite the high incidence, biomarkers for OC diagnosis are lacking and consequently, patients are often diagnosed in advanced stages. This delay in diagnosis is reflected by poor overall outcomes of OC patients, where 5-year overall survival is around 50%. Among the biomarkers proposed for cancer detection, noncoding RNA (ncRNA) can be considered as one of the most promising categories of biomarkers due to their role in virtually all cellular processes. Similar to other cancer types, changes in expressions of ncRNAs have been reported in OC and a number of ncRNAs have diagnostic, prognostic, and therapeutic potential. Moreover, some ncRNAs are capable of regulating gene expression by various mechanisms. Therefore, elucidating the current literature on the four main types of ncRNAs namely, microRNA, lncRNA, snoRNA, piwi-RNA, and circular RNA in the context of OC pathogenesis is timely and would enable further improvements and innovations in diagnosis, prognosis, and treatment of OC. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA in Disease and Development > RNA in Development.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10909450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10051352","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}
Pub Date : 2023-05-01Epub Date: 2022-09-19DOI: 10.1002/wrna.1762
Geneva R LaForce, Polyxeni Philippidou, Ashleigh E Schaffer
Balanced mRNA isoform diversity and abundance are spatially and temporally regulated throughout cellular differentiation. The proportion of expressed isoforms contributes to cell type specification and determines key properties of the differentiated cells. Neurons are unique cell types with intricate developmental programs, characteristic cellular morphologies, and electrophysiological potential. Neuron-specific gene expression programs establish these distinctive cellular characteristics and drive diversity among neuronal subtypes. Genes with neuron-specific alternative processing are enriched in key neuronal functions, including synaptic proteins, adhesion molecules, and scaffold proteins. Despite the similarity of neuronal gene expression programs, each neuronal subclass can be distinguished by unique alternative mRNA processing events. Alternative processing of developmentally important transcripts alters coding and regulatory information, including interaction domains, transcript stability, subcellular localization, and targeting by RNA binding proteins. Fine-tuning of mRNA processing is essential for neuronal activity and maintenance. Thus, the focus of neuronal RNA biology research is to dissect the transcriptomic mechanisms that underlie neuronal homeostasis, and consequently, predispose neuronal subtypes to disease. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA in Disease and Development > RNA in Development.
{"title":"mRNA isoform balance in neuronal development and disease.","authors":"Geneva R LaForce, Polyxeni Philippidou, Ashleigh E Schaffer","doi":"10.1002/wrna.1762","DOIUrl":"10.1002/wrna.1762","url":null,"abstract":"<p><p>Balanced mRNA isoform diversity and abundance are spatially and temporally regulated throughout cellular differentiation. The proportion of expressed isoforms contributes to cell type specification and determines key properties of the differentiated cells. Neurons are unique cell types with intricate developmental programs, characteristic cellular morphologies, and electrophysiological potential. Neuron-specific gene expression programs establish these distinctive cellular characteristics and drive diversity among neuronal subtypes. Genes with neuron-specific alternative processing are enriched in key neuronal functions, including synaptic proteins, adhesion molecules, and scaffold proteins. Despite the similarity of neuronal gene expression programs, each neuronal subclass can be distinguished by unique alternative mRNA processing events. Alternative processing of developmentally important transcripts alters coding and regulatory information, including interaction domains, transcript stability, subcellular localization, and targeting by RNA binding proteins. Fine-tuning of mRNA processing is essential for neuronal activity and maintenance. Thus, the focus of neuronal RNA biology research is to dissect the transcriptomic mechanisms that underlie neuronal homeostasis, and consequently, predispose neuronal subtypes to disease. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA in Disease and Development > RNA in Development.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10024649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10035871","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}
Kundan Kumar, Shubham Kumar Sinha, Upasana Maity, Pulugurtha Bharadwaja Kirti, Koppolu Raja Rajesh Kumar
Splicing of pre-mRNA is an essential part of eukaryotic gene expression. Serine-/arginine-rich (SR) proteins are highly conserved RNA-binding proteins present in all metazoans and plants. SR proteins are involved in constitutive and alternative splicing, thereby regulating the transcriptome and proteome diversity in the organism. In addition to their role in splicing, SR proteins are also involved in mRNA export, nonsense-mediated mRNA decay, mRNA stability, and translation. Due to their pivotal roles in mRNA metabolism, SR proteins play essential roles in normal growth and development. Hence, any misregulation of this set of proteins causes developmental defects in both plants and animals. SR proteins from the animal kingdom are extensively studied for their canonical and noncanonical functions. Compared with the animal kingdom, plant genomes harbor more SR protein-encoding genes and greater diversity of SR proteins, which are probably evolved for plant-specific functions. Evidence from both plants and animals confirms the essential role of SR proteins as regulators of gene expression influencing cellular processes, developmental stages, and disease conditions. This article is categorized under: RNA Processing > Splicing Mechanisms RNA Processing > Splicing Regulation/Alternative Splicing.
{"title":"Insights into established and emerging roles of SR protein family in plants and animals.","authors":"Kundan Kumar, Shubham Kumar Sinha, Upasana Maity, Pulugurtha Bharadwaja Kirti, Koppolu Raja Rajesh Kumar","doi":"10.1002/wrna.1763","DOIUrl":"https://doi.org/10.1002/wrna.1763","url":null,"abstract":"<p><p>Splicing of pre-mRNA is an essential part of eukaryotic gene expression. Serine-/arginine-rich (SR) proteins are highly conserved RNA-binding proteins present in all metazoans and plants. SR proteins are involved in constitutive and alternative splicing, thereby regulating the transcriptome and proteome diversity in the organism. In addition to their role in splicing, SR proteins are also involved in mRNA export, nonsense-mediated mRNA decay, mRNA stability, and translation. Due to their pivotal roles in mRNA metabolism, SR proteins play essential roles in normal growth and development. Hence, any misregulation of this set of proteins causes developmental defects in both plants and animals. SR proteins from the animal kingdom are extensively studied for their canonical and noncanonical functions. Compared with the animal kingdom, plant genomes harbor more SR protein-encoding genes and greater diversity of SR proteins, which are probably evolved for plant-specific functions. Evidence from both plants and animals confirms the essential role of SR proteins as regulators of gene expression influencing cellular processes, developmental stages, and disease conditions. This article is categorized under: RNA Processing > Splicing Mechanisms RNA Processing > Splicing Regulation/Alternative Splicing.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9668804","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}
Pub Date : 2023-05-01Epub Date: 2022-08-14DOI: 10.1002/wrna.1757
Chioniso Patience Masamha
The mammalian cleavage factor I subunit CFIm25 (NUDT21) binds to the UGUA sequences of precursor RNAs. Traditionally, CFIm25 is known to facilitate 3' end formation of pre-mRNAs resulting in the formation of polyadenylated transcripts. Recent studies suggest that CFIm25 may be involved in the cyclization and hence generation of circular RNAs (circRNAs) that contain UGUA motifs. These circRNAs act as competing endogenous RNAs (ceRNAs) that disrupt the ceRNA-miRNA-mRNA axis. Other emerging roles of CFIm25 include regulating both alternative splicing and alternative polyadenylation (APA). APA generates different sized transcripts that may code for different proteins, or more commonly transcripts that code for the same protein but differ in the length and sequence content of their 3' UTRs (3' UTR-APA). CFIm25 mediated global changes in 3' UTR-APA affect human physiology including spermatogenesis and the determination of cell fate. Deregulation of CFIm25 and changes in 3' UTR-APA have been implicated in several human diseases including cancer. In many cancers, CFIm25 acts as a tumor suppressor. However, there are some cancers where CFIm25 has the opposite effect. Alterations in CFIm25-driven 3' UTR-APA may also play a role in neural dysfunction and fibrosis. CFIm25 mediated 3' UTR-APA changes can be used to generate specific signatures that can be used as potential biomarkers in development and disease. Due to the emerging role of CFIm25 as a regulator of the aforementioned RNA processing events, modulation of CFIm25 levels may be a novel viable therapeutic approach. This article is categorized under: RNA Processing > 3' End Processing RNA in Disease and Development > RNA in Disease.
{"title":"The emerging roles of CFIm25 (NUDT21/CPSF5) in human biology and disease.","authors":"Chioniso Patience Masamha","doi":"10.1002/wrna.1757","DOIUrl":"10.1002/wrna.1757","url":null,"abstract":"<p><p>The mammalian cleavage factor I subunit CFIm25 (NUDT21) binds to the UGUA sequences of precursor RNAs. Traditionally, CFIm25 is known to facilitate 3' end formation of pre-mRNAs resulting in the formation of polyadenylated transcripts. Recent studies suggest that CFIm25 may be involved in the cyclization and hence generation of circular RNAs (circRNAs) that contain UGUA motifs. These circRNAs act as competing endogenous RNAs (ceRNAs) that disrupt the ceRNA-miRNA-mRNA axis. Other emerging roles of CFIm25 include regulating both alternative splicing and alternative polyadenylation (APA). APA generates different sized transcripts that may code for different proteins, or more commonly transcripts that code for the same protein but differ in the length and sequence content of their 3' UTRs (3' UTR-APA). CFIm25 mediated global changes in 3' UTR-APA affect human physiology including spermatogenesis and the determination of cell fate. Deregulation of CFIm25 and changes in 3' UTR-APA have been implicated in several human diseases including cancer. In many cancers, CFIm25 acts as a tumor suppressor. However, there are some cancers where CFIm25 has the opposite effect. Alterations in CFIm25-driven 3' UTR-APA may also play a role in neural dysfunction and fibrosis. CFIm25 mediated 3' UTR-APA changes can be used to generate specific signatures that can be used as potential biomarkers in development and disease. Due to the emerging role of CFIm25 as a regulator of the aforementioned RNA processing events, modulation of CFIm25 levels may be a novel viable therapeutic approach. This article is categorized under: RNA Processing > 3' End Processing RNA in Disease and Development > RNA in Disease.</p>","PeriodicalId":23886,"journal":{"name":"Wiley Interdisciplinary Reviews: RNA","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9925614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10051353","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}