Article
Biochemistry & Molecular Biology
Jihae Shin, Qingbao Ding, Luyang Wang, Yange Cui, Erdene Baljinnyam, Aysegul Guvenek, Bin Tian
Summary: APA is an important aspect of gene expression program critical for defining cell identity. A method named CRISPRpas, which enhances proximal PAS usage, is developed to alter APA isoform abundance. The efficiency of CRISPRpas is influenced by various factors. The study demonstrates the modulation of APA for multiple endogenous genes and highlights the impact of CRISPRpas on gene expression.
NUCLEIC ACIDS RESEARCH
(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
Biochemistry & Molecular Biology
Katarzyna Taylor, Agnieszka Piasecka, Arkadiusz Kajdasz, Aleksandra Brzek, Micaela Polay Espinoza, Cyril F. Bourgeois, Artur Jankowski, Malgorzata Borowiak, Katarzyna D. Raczynska, Lukasz J. Sznajder, Krzysztof Sobczak
Summary: This study aims to elucidate the mechanism of muscleblind-like splicing regulators (MBNLs) in alternative splicing (AS) processes. The findings indicate that DEAD-box (DDX) RNA helicases DDX5 and DDX17 play an important role in MBNL-dependent AS regulation. The helicases modulate MBNL splicing activity through changes in the ratio of MBNL splicing isoforms and accessibility of MBNL-binding sites. These findings contribute to a deeper understanding of the interdependencies between RNA-binding proteins and their implications in developmental homeostasis and pathological states.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Siyao Guo, Shuibin Lin
Summary: mRNA polyadenylation plays a crucial role in regulating mRNA metabolism. Mis-regulation of mRNA polyadenylation is often associated with abnormal gene expression and disease progression. This review summarizes the classical process of mRNA 3'-terminal formation, discusses the mechanisms of poly(A) length control in the nucleus and cytoplasm, reviews the progress in alternative polyadenylation regulation and APA site selection mechanism, and finally summarizes the functional roles of APA in gene expression regulation and diseases including cancers.
Review
Genetics & Heredity
Lu Wei, Eric C. Lai
Summary: The process of APA can alter regulatory capacity and coding potential of genes, leading to the formation of characteristic 3' UTR isoforms in neurons. However, our understanding of APA mechanisms and biology is still limited.
FRONTIERS IN GENETICS
(2022)
Review
Cell Biology
Prakash Dharmalingam, Rajasekaran Mahalingam, Hari Krishna Yalamanchili, Tingting Weng, Harry Karmouty-Quintana, Ashrith Guha, Rajarajan A. Thandavarayan
Summary: Research has shown that alternative cleavage and polyadenylation (APA) play a crucial role in the pathogenesis of various human diseases, leading to dysfunctional gene regulation and abnormal cell proliferation. While the functions of the core APA machinery and its role in disease conditions remain largely unknown, the mechanism of APA has become a hot topic in disease research.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Wendy V. Gilbert, Sigrid Nachtergaele
Summary: Chemical modifications on mRNA play a crucial role in gene expression regulation, and research in this area has been rapidly advancing in the past decade. mRNA modifications have been found to influence various stages of mRNA life cycle, but the underlying molecular mechanisms are still not fully understood. This article summarizes recent studies that have shed light on the roles of mRNA modifications, identifies knowledge gaps and unanswered questions, and provides insights for future research directions in this field.
ANNUAL REVIEW OF BIOCHEMISTRY
(2023)
Article
Plant Sciences
Ping Lu, Daipeng Chen, Zhaomei Qi, Haoming Wang, Yitong Chen, Qinhu Wang, Cong Jiang, Jin-Rong Xu, Huiquan Liu
Summary: This study investigates the landscape and regulation of alternative splicing (AS) and alternative polyadenylation (APA) in Fusarium graminearum, a filamentous fungus. The results reveal that AS and APA play important roles in gene expression regulation, with the majority of AS events affecting coding sequences. Unexpectedly, AS transcripts with premature-termination codons are not degraded. Distal APA sites have strong signals, while proximal APA isoforms are highly expressed in F. graminearum. The study also uncovers the roles of 3'-end processing factors in promoting proximal APA site usage and intron splicing. Furthermore, the study suggests intron inclusion and 3'-untranslated region lengthening as novel mechanisms in regulating aging and dormancy in fungi.
Article
Biology
Sibylle Mitschka, Christine Mayr
Summary: The study discovered that the endogenous 3'UTR does not play a role in regulating p53 expression in tumors. CRISPR/Cas9 experiments revealed this phenomenon while also confirming the repressive effects of the 3'UTR.
Article
Biochemistry & Molecular Biology
Luis Alberto Rivera-Rivas, Rossana Arroyo
Summary: This study aims to explore the posttranscriptional regulatory mechanism of the TvCP2 gene in Trichomonas vaginalis under iron-limited conditions. The stability of tvcp2 mRNA was found to be higher under iron-restricted conditions compared to high iron conditions. Two isoforms of tvcp2 mRNA with different 3'-UTR were demonstrated, leading to more TvCP2 protein under iron-restricted conditions. In silico analysis identified 16 genes that may be involved in trichomonad polyadenylation machinery, and most of these genes were shown to be positively regulated by iron according to qRT-PCR assays. Therefore, our results suggest the presence of alternative polyadenylation as a novel iron posttranscriptional regulatory mechanism in T. vaginalis for the tvcp2 gene expression.
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
(2023)
Article
Biochemistry & Molecular Biology
Alina Chakraborty, Mandy Cadix, Sebastien Relier, Nicolo Taricco, Tina Alaeitabar, Alexandre Devaux, Celine M. Labbe, Sylvain Martineau, Amelie Heneman-Masurel, Pierre Gestraud, Alberto Inga, Nicolas Servant, Stephan Vagner, Martin Dutertre
Summary: This study reveals differential regulation of intronic polyadenylation (IPA) isoform ratio across subcellular compartments during drug response, suggesting distinct patterns of IPA isoform regulation in the transcriptome and translatome, as well as between the nucleus and cytosol.
Article
Neurosciences
Aidong Yuan, Ralph A. Nixon
Summary: Neurofilament and tau proteins are involved in regulating stability and functions of the microtubule network in axons, axonal transport, and learning and memory. Their expression is regulated at the transcriptional and posttranscriptional levels, with RNA-binding proteins and microRNAs playing important roles in their regulation through the 3'-untranslated regions of their mRNA.
BRAIN RESEARCH BULLETIN
(2023)
Review
Biochemistry & Molecular Biology
Lulu Yu, Vladimir Majerciak, Zhi-Ming Zheng
Summary: Human papillomaviruses (HPV) are a group of viruses that cause cancer, with HPV16 and HPV18 being the most common types responsible for majority of cases. The expression of their genome is regulated by alternative RNA splicing, and epigenetic modifications also play a role in HPV infections and carcinogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Plant Sciences
Hui Ma, Lingling Cai, Juncheng Lin, Kaiyue Zhou, Qingshun Q. Li
Summary: Salt tolerance is an important mechanism for plants to adapt to a saline environment. Through global analyses of mRNA alternative polyadenylation (APA), researchers found that Arabidopsis thaliana and its halophytic relative Eutrema salsugineum have different responses to salt stress. Arabidopsis is more sensitive to salt stress, while Eutrema exhibits an innate response to such conditions. The number of APA genes and the enriched pathways in response to salt stress also differ between the two species.
FRONTIERS IN PLANT SCIENCE
(2022)
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
Oncology
Keqiang Chen, Teizo Yoshimura, Xiaohong Yao, Wanghua Gong, Jiaqiang Huang, Amiran K. Dzutsev, John McCulloch, Colm O'hUigin, Xiu-wu Bian, Giorgio Trinchieri, Ji Ming Wang
Summary: CRAMP plays a protective role in the mouse colon against inflammation, inflammation-associated carcinogenesis, and disrupted microbiome balance. Epithelial cell-derived CRAMP is crucial for normal development and repair of colon crypts, while myeloid cell-derived CRAMP enhances colon epithelial resistance to bacterial invasion during acute inflammation.
JOURNAL OF PATHOLOGY
(2021)
Article
Medical Laboratory Technology
G. Oree, M. Naicker, H. C. Maise, P. Tinarwo, V Ramsuran, N. S. Abbai
Summary: This study aimed at detecting antimicrobial-resistant determinants in Neisseria gonorrhoeae directly from endocervical specimens. Results showed that tetM gene carried on the American-type plasmid was present in all specimens, approximately 87.5% of specimens carried penicillinase-producing African-type plasmid, and 37.5% of specimens carried the gyrase A gene with the Ser-91 mutation.
LABORATORY MEDICINE
(2022)
Article
Environmental Sciences
Pragalathan Naidoo, Terisha Ghazi, Anil A. Chuturgoon, Rajen N. Naidoo, Veron Ramsuran, Miranda N. Mpaka-Mbatha, Khethiwe N. Bhengu, Nomzamo Nembe, Zamathombeni Duma, Roxanne Pillay, Ravesh Singh, Zilungile L. Mkhize-Kwitshanaa
Summary: Soil-transmitted helminths infect billions globally, with poor environmental sanitation and pollution exacerbating the hyper-inflammatory immune response to SARS-CoV-2. Helminth-induced Th2/Th3 immune response may protect against lung damage but could be hindered by air pollutants overexpressing ACE2 receptors. Further studies are needed to understand the complex interactions between helminths, air pollution, and SARS-CoV-2.
ENVIRONMENT INTERNATIONAL
(2021)
Article
Genetics & Heredity
Arman A. Bashirova, Wanjing Zheng, Marjan Akdag, Danillo G. Augusto, Nicolas Vince, Krista L. Dong, Colm O'hUigin, Mary Carrington
Summary: Human IgG molecules, including IgG1, IgG2, and IgG3, exhibit significant inter-individual variation in their constant heavy chain regions, which may influence antibody function. Variation in IGHG2 and IGHG3 genes is higher in individuals of African descent compared to European descent. The study provides a comprehensive analysis of IgG polymorphisms across major populations, which can be used to decipher their functional impact.
GENES AND IMMUNITY
(2021)
Article
Microbiology
Vinicius Adriano Vieira, Emily Adland, David F. G. Malone, Maureen P. Martin, Andreas Groll, M. Azim Ansari, Maria C. Garcia-Guerrero, Mari C. Puertas, Maximilian Muenchhoff, Claudia Fortuny Guash, Christian Brander, Javier Martinez-Picado, Alasdair Bamford, Gareth Tudor-Williams, Thumbi Ndung'u, Bruce D. Walker, Veron Ramsuran, John Frater, Pieter Jooste, Dimitra Peppa, Mary Carrington, Philip J. R. Goulder
Summary: This study reveals the significant contribution of NK cell responses to immune control of HIV in children. Children living with HIV show better viraemic control and disease progression when they have a genetic signature favoring KIR-education on NK cells. The less differentiated NKG2A+NKp46+CD56dim NK cell population, highly responsive to cytokine stimulation, plays a crucial role in controlling HIV viraemia in children.
Review
Immunology
Thilona Arumugam, Upasana Ramphal, Theolan Adimulam, Romona Chinniah, Veron Ramsuran
Summary: This review focuses on the impact of HIV infection on the expression of DNA methylation modifying factors, the effect of DNA methylation on HIV viral and host genes, as well as the potential of DNA methylation as an epigenetic therapeutic strategy and biomarker. Despite new drugs for HIV and genetic therapies being investigated, alternative nongenetic therapies like DNA methylation are essential.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Microbiology
Nireshni Mitchev, Ravesh Singh, Veron Ramsuran, Arshad Ismail, Mushal Allam, Stanford Kwenda, Florah Mnyameni, Nigel Garrett, Khine Swe Swe-Han, Abraham J. Niehaus, Koleka P. Mlisana
Summary: This study aimed to detect genetic mutations and plasmids associated with antimicrobial resistance in Neisseria gonorrhoeae isolates from patients in South Africa using real-time PCR. The results showed that the real-time PCR method accurately identified all N. gonorrhoeae-positive samples and showed good correlation with traditional culture methods. These findings provide a basis for the development of convenient culture-free diagnostic tools in the future.
INTERNATIONAL JOURNAL OF MICROBIOLOGY
(2022)
Article
Microbiology
Nireshni Mitchev, Ravesh Singh, Veron Ramsuran, Arshad Ismail, Mushal Allam, Stanford Kwenda, Florah Mnyameni, Nigel Garrett, Khine Swe Swe-Han, Abraham J. J. Niehaus, Koleka P. P. Mlisana
Summary: This study in clinical isolates from KwaZulu-Natal, South Africa investigated the correlation of mRNA expression levels in Neisseria gonorrhoeae antibiotic target genes and efflux pump genes with antibiotic resistance. The study identified specific markers such as mtrC, gyrA, parE, rpsJ, and 23S rRNA, which could be used to predict resistance and guide patient management in a cost-effective manner through real-time qPCR.
INTERNATIONAL JOURNAL OF MICROBIOLOGY
(2022)
Article
Genetics & Heredity
Arman A. Bashirova, Wojciech Kasprzak, Colm O'hUigin, Mary Carrington
Summary: The genes LILRB3 and LILRA6 encode homologous receptors with inhibitory and activating functions, respectively. These genes exhibit high levels of polymorphism at the amino acid level, and LILRA6 shows variation in copy number. By analyzing the genetic variation in 91 individuals, it was found that common alleles of LILRB3 and LILRA6 encode different amino acid sequences in homologous regions, potentially affecting their functions differently. Furthermore, the comparison of sequences in individuals with different copy numbers of LILRA6 suggests a mechanism of non-allelic homologous recombination between LILRB3 and LILRA6. These findings provide a detailed characterization of LILRB3/LILRA6 genetic variation and highlight the need for determining their ligands.
Review
Biochemistry & Molecular Biology
Theolan Adimulam, Thilona Arumugam, Anmol Gokul, Veron Ramsuran
Summary: The novel coronavirus, SARS-CoV-2, has become a global pandemic with high infectivity and mortality. Studies have found genetic effects on disease severity of SARS-CoV-2 within Eurasian populations, but contrasting effects in African populations. Genetic factors, such as single nucleotide polymorphisms (SNPs) in the receptor genes, can explain the diversity in disease susceptibility and severity. This study examined SNPs in four SARS-CoV-2 receptors and highlighted the importance of further genetic research in African populations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Genetics & Heredity
Phakamani Goodman Mthethwa, Leonard Charles Marais, Veron Ramsuran, Collen Michelle Aldous
Summary: This systematic review examines the genetic alterations of molecular biomarkers associated with multidrug chemotherapy resistance in osteosarcoma. Six studies were included in the qualitative analysis, identifying 473 differentially expressed genes (DEGs) associated with chemotherapy response in high-grade conventional osteosarcoma (COS). Among them, 57 genes were associated with multidrug resistance (MDR) in osteosarcoma. The heterogeneous gene expressions were related to the mechanism of MDR in osteosarcoma, including drug-related sensitivity genes, bone remodelling, and signal transduction.
Review
Genetics & Heredity
Anmol Gokul, Thilona Arumugam, Veron Ramsuran
Summary: In recent studies, it has been found that infectious diseases are more prevalent in Africa. This is partly due to unique genetic variants found within the African genome. Understanding the host genetic mechanisms can help develop targeted therapies for these diseases.
Article
Genetics & Heredity
Theolan Adimulam, Thilona Arumugam, Anushka Naidoo, Kogieleum Naidoo, Veron Ramsuran
Summary: Human gene mutations in specific genes have been shown to be associated with variable outcomes of COVID-19. This study investigates the role of specific polymorphisms in ACE2, TMPRSS2, NRP1, and CD147 in COVID-19 severity and viral load. The results demonstrate an ethnic bias in the association between the rs2285666 variant and COVID-19 severity, and significant associations between rs2285666 and rs10080 variants and increased viral load and worse outcomes in certain ethnicities. Additionally, the study finds that the SARS-CoV-2 viral load is significantly lower in Africans compared to individuals of European and South Asian descent. The findings highlight the genetic basis for differences in COVID-19 severity across ethnic groups in South Africa.
Article
Medicine, Research & Experimental
Nireshni Mitchev, Ravesh Singh, Nigel Garrett, Veron Ramsuran, Abraham J. Niehaus, Koleka P. Mlisana
Summary: Through testing in a cohort of South African women, our multiple singleplex PCR strategy has been shown to be a simple, accurate, rapid, affordable, and scalable option for diagnosing VDS.
AFRICAN JOURNAL OF LABORATORY MEDICINE
(2021)
Article
Microbiology
Nireshni Mitchev, Mushal Allam, Stanford Kwenda, Florah Mnyameni, Arshad Ismail, Abraham J. Niehaus, Veron Ramsuran, Nigel Garrett, Ravesh Singh, Koleka P. Mlisana
Summary: Africa has the highest incidence of Neisseria gonorrhoeae infections globally, but data on these isolates is scarce. Here, we report six N. gonorrhoeae genome sequences with five novel sequence types isolated from patients with uncomplicated genitourinary gonorrhea in South Africa.
MICROBIOLOGY RESOURCE ANNOUNCEMENTS
(2021)