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REVIEW
Yoona Seo, Jiho Rhim, Jong Heon Kim
Recent progress in the investigation of microRNA (miRNA) biogenesis and the miRNA processing machinery has revealed previously unknown roles of posttranscriptional regulation in gene expression. The molecular mechanistic interplay between miRNAs and their regulatory factors, RNA-binding proteins (RBPs) and exoribonucleases, has been revealed to play a critical role in tumorigenesis. Moreover, recent studies have shown that the proliferation of hepatocellular carcinoma (HCC)-causing hepatitis C virus (HCV) is also characterized by close crosstalk of a multitude of host RBPs and exoribonucleases with miR-122 and its RNA genome, suggesting the importance of the mechanistic interplay among these factors during the proliferation of HCV...
May 1, 2024: Experimental & Molecular Medicine
#2
JOURNAL ARTICLE
Mrinmoyee Majumder, Harinarayanan Janakiraman, Paramita Chakraborty, Anitha Vijayakumar, Sari Mayhue, Hong Yu, Toros Dincman, Romeo Martin, Elizabeth O'Quinn, Shikhar Mehrotra, Viswanathan Palanisamy
Hu Antigen R, also known as ELAVL1 (HuR), is a key posttranscriptional regulator in eukaryotic cells. HuR overexpression promotes several malignancies, including head and neck squamous cell carcinoma (HNSCC). However, its immune dysfunction-associated tumorigenesis pathways remain unknown. We examined HuR's effects on oral malignancies and immune cell function in vitro and in vivo using oral carcinoma cells and transgenic HuR knockout (KO) mice. CRISPR/Cas9-mediated HuR deletion in mice syngeneic oral cancer cells eliminated colony formation and tumor development...
June 2024: Oral Oncol Rep
#3
REVIEW
Nives Pećina-Šlaus, Reno Hrašćan
On a molecular level, glioma is very diverse and presents a whole spectrum of specific genetic and epigenetic alterations. The tumors are unfortunately resistant to available therapies and the survival rate is low. The explanation of significant intra- and inter-tumor heterogeneity and the infiltrative capability of gliomas, as well as its resistance to therapy, recurrence and aggressive behavior, lies in a small subset of tumor-initiating cells that behave like stem cells and are known as glioma cancer stem cells (GCSCs)...
April 19, 2024: Cancers
#4
JOURNAL ARTICLE
Kevin T Militello, Jennifer Leigh, Matthew Pusateri, Laurie K Read, Dineen Vogler
In Trypanosoma brucei, gene expression is primarily regulated posttranscriptionally making RNA metabolism critical. T. brucei has an epitranscriptome containing modified RNA bases. Yet, the identity of the enzymes catalyzing modified RNA base addition and the functions of the enzymes and modifications remain unclear. Homology searches indicate the presence of numerous T. brucei cytosine RNA methyltransferase homologs. One such homolog, TbNop2 was studied in detail. TbNop2 contains the six highly conserved motifs found in cytosine RNA methyltransferases and is evolutionarily related to the Nop2 protein family required for rRNA modification and processing...
2024: PloS One
#5
JOURNAL ARTICLE
Alba R Díez, Dóra Szakonyi, Jorge Lozano-Juste, Paula Duque
Abscisic acid (ABA) is a crucial player in plant responses to the environment. It accumulates under stress, activating downstream signaling to implement molecular responses that restore homeostasis. Natural variance in ABA sensitivity remains barely understood, and the ABA pathway has been mainly studied at the transcriptional level, despite evidence that posttranscriptional regulation, namely, via alternative splicing, contributes to plant stress tolerance. Here, we identified the Arabidopsis accession Kn-0 as less sensitive to ABA than the reference Col-0, as shown by reduced effects of the hormone on seedling establishment, root branching, and stomatal closure, as well as by decreased induction of ABA marker genes...
April 25, 2024: Plant Journal
#6
REVIEW
Sonia Gazzarrini, Liang Song
Development is a chain reaction in which one event leads to another until the completion of a life cycle. Phase transitions are milestone events in the cycle of life. LEAFY COTYLEDON1 (LEC1), ABA INSENSITIVE3 (ABI3), FUSCA3 (FUS3), and LEC2 proteins, collectively known as LAFL, are master transcription factors (TFs) regulating seed and other developmental processes. Since the initial characterization of the LAFL genes (44, 71, 98-100), more than three decades of active research has generated tremendous amounts of knowledge about these TFs, whose roles in seed development and germination have been comprehensively reviewed (63, 43, 65, 81)...
April 24, 2024: Annual Review of Plant Biology
#7
JOURNAL ARTICLE
Ningheng Chen, Shiyong Wu, Kangkang Zhi, Xiaoping Zhang, Xueli Guo
The RNA-binding zinc finger protein 36 (ZFP36) family participates in numerous physiological processes including transition and differentiation through post-transcriptional regulation. ZFP36L1 is a member of the ZFP36 family. This study aimed to evaluate the role of ZFP36L1 in restenosis. We found that the expression of ZFP36L1 was inhibited in VSMC-phenotypic transformation induced by TGF-β, PDGF-BB, and FBS and also in the rat carotid injury model. In addition, we found that the overexpression of ZFP36L1 inhibited the proliferation and migration of VSMCs and promoted the expression of VSMC contractile genes; whereas ZFP36L1 interference promoted the proliferation and migration of VSMCs and suppressed the expression of contractile genes...
April 21, 2024: Journal of Molecular and Cellular Cardiology
#8
JOURNAL ARTICLE
Bilal Murtaza, Xiaoyu Li, Muhammad Yasir Nawaz, Muhammad Kashif Saleemi, Gen Li, Bowen Jin, Lili Wang, Yongping Xu
Mycotoxins, ubiquitous contaminants in food, present a global threat to human health and well-being. Mitigation efforts, such as the implementation of sound agricultural practices, thorough food processing, and the advancement of mycotoxin control technologies, have been instrumental in reducing mycotoxin exposure and associated toxicity. To comprehensively assess mycotoxins and their toxicodynamic implications, the deployment of effective and predictive strategies is imperative. Understanding the manner of action, transformation, and cumulative toxic effects of mycotoxins, moreover, their interactions with food matrices can be gleaned through gene expression and transcriptome analyses at cellular and molecular levels...
May 2024: Comprehensive Reviews in Food Science and Food Safety
#9
JOURNAL ARTICLE
Julian J Freen-van Heeren
Maintaining immune homeostasis is instrumental for host health. Immune cells, such as T cells, are instrumental for the eradication of pathogenic bacteria, fungi and viruses. Furthermore, T cells also play a major role in the fight against cancer. Through the formation of immunological memory, a pool of antigen-experienced T cells remains in the body to rapidly protect the host upon reinfection or retransformation. In order to perform their protective function, T cells produce cytolytic molecules, such as granzymes and perforin, and cytokines such as interferon γ and tumor necrosis factor α...
2024: Methods in Molecular Biology
#10
JOURNAL ARTICLE
Hao Zheng, Zhuo Cao, Yuankai Lv, Xiaoping Cai
N6-methyladenosine (m6A) is a common posttranscriptional RNA modification and plays an important role in cancer biology. Circular RNAs (circRNAs) are also reported to participate in lung adenocarcinoma (LUAD) progression. Here, we aimed to investigate the functions of Wilms tumor 1-associating protein (WTAP) methyltransferase and circEEF2 in LUAD cell tumorigenesis, and probe whether circEEF2 functioned through WTAP-induced m6A modification and its potential mechanisms. Functional analyses were conducted by tube formation, sphere formation, 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, and transwell assays in vitro as well as tumor formation experiments in mice, respectively...
April 15, 2024: Molecular Biotechnology
#11
JOURNAL ARTICLE
Hyemin Lee, Li Zhuang, Boyi Gan
N6-Methyladenosine (m6A), a prevalent posttranscriptional modification, plays an important role in cancer progression. Clear cell renal cell carcinoma (ccRCC) is chiefly associated with the loss of the von Hippel-Lindau (VHL) gene, encoding a component of the E3 ubiquitin ligase complex. In this issue of the JCI, Zhang and colleagues unveiled a function of VHL beyond its canonical role as an E3 ubiquitin ligase in regulating hypoxia-inducible factors (HIFs). It also governed m6A modification by orchestrating the assembly of m6A writer proteins METTL3 and METTL14, thereby stabilizing PIK3R3 mRNA...
April 15, 2024: Journal of Clinical Investigation
#12
JOURNAL ARTICLE
Cheng Zhang, Miaomiao Yu, Austin J Hepperla, Zhao Zhang, Rishi Raj, Hua Zhong, Jin Zhou, Lianxin Hu, Jun Fang, Hongyi Liu, Qian Liang, Liwei Jia, Chengheng Liao, Sichuan Xi, Jeremy M Simon, Kexin Xu, Zhijie Liu, Yunsun Nam, Payal Kapur, Qing Zhang
N6-Methyladenosine (m6A) is the most abundant posttranscriptional modification, and its contribution to cancer evolution has recently been appreciated. Renal cancer is the most common adult genitourinary cancer, approximately 85% of which is accounted for by the clear cell renal cell carcinoma (ccRCC) subtype characterized by VHL loss. However, it is unclear whether VHL loss in ccRCC affects m6A patterns. In this study, we demonstrate that VHL binds and promotes METTL3/METTL14 complex formation while VHL depletion suppresses m6A modification, which is distinctive from its canonical E3 ligase role...
April 15, 2024: Journal of Clinical Investigation
#13
REVIEW
Fabian Stahl, Bernd O Evert, Xinyu Han, Peter Breuer, Ullrich Wüllner
The spinocerebellar ataxias (SCA) comprise a group of inherited neurodegenerative diseases. Machado-Joseph Disease (MJD) or spinocerebellar ataxia 3 (SCA3) is the most common autosomal dominant form, caused by the expansion of CAG repeats within the ataxin-3 (ATXN3) gene. This mutation results in the expression of an abnormal protein containing long polyglutamine (polyQ) stretches that confers a toxic gain of function and leads to misfolding and aggregation of ATXN3 in neurons. As a result of the neurodegenerative process, SCA3 patients are severely disabled and die prematurely...
April 3, 2024: International Journal of Molecular Sciences
#14
JOURNAL ARTICLE
S Cortes, E Farhat, Ggm Talarico, J A Mennigen
Oxygen is essential to fuel aerobic metabolism. Some species evolved mechanisms to tolerate periods of severe hypoxia and even anoxia in their environment. Among them, goldfish (Carassius auratus) are unique, in that they do not enter a comatose state under severely hypoxic conditions. There is thus significant interest in the field of comparative physiology to uncover the mechanistic basis underlying hypoxia tolerance in goldfish, with a particular focus on the brain. Taking advantage of the recently published and annotated goldfish genome, we profile the transcriptomic response of the goldfish brain under normoxic (21 kPa oxygen saturation) and, following gradual reduction, constant hypoxic conditions after 1 and 4 weeks (2...
April 9, 2024: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
#15
JOURNAL ARTICLE
Paula Ayuso-García, Alejandro Sánchez-Rueda, Sergio Velasco-Avilés, Miguel Tamayo-Caro, Aroa Ferrer-Pinós, Cecilia Huarte-Sebastian, Vanesa Alvarez, Cristina Riobello, Selene Jiménez-Vega, Izaskun Buendia, Jorge Cañas-Martin, Héctor Fernández-Susavila, Adrián Aparicio-Rey, Eva M Esquinas-Román, Carlos Rodríguez Ponte, Romane Guhl, Nicolas Laville, Encarni Pérez-Andrés, José L Lavín, Monika González-Lopez, Nuria Macías Cámara, Ana M Aransay, Juan José Lozano, James D Sutherland, Rosa Barrio, María Luz Martinez-Chantar, Mikel Azkargorta, Félix Elortza, Mario Soriano-Navarro, Carlos Matute, María Victoria Sánchez-Gómez, Laura Bayón-Cordero, Alberto Pérez-Samartín, Susana B Bravo, Thimo Kurz, Tomas Lama-Díaz, Miguel G Blanco, Saif Haddad, Christopher J Record, Peter M van Hasselt, Mary M Reilly, Marta Varela-Rey, Ashwin Woodhoo
Myelination is essential for neuronal function and health. In peripheral nerves, >100 causative mutations have been identified that cause Charcot-Marie-Tooth disease, a disorder that can affect myelin sheaths. Among these, a number of mutations are related to essential targets of the posttranslational modification neddylation, although how these lead to myelin defects is unclear. Here, we demonstrate that inhibiting neddylation leads to a notable absence of peripheral myelin and axonal loss both in developing and regenerating mouse nerves...
April 12, 2024: Science Advances
#16
JOURNAL ARTICLE
Najeeb U Siddiqui, Angelo Karaiskakis, Aaron L Goldman, Whitby V I Eagle, Timothy C H Low, Hua Luo, Craig A Smibert, Elizabeth R Gavis, Howard D Lipshitz
During Drosophila oogenesis, the Oskar (OSK) RNA binding protein (RBP) determines the amount of germ plasm that assembles at the posterior pole of the oocyte. Here, we identify mechanisms that subsequently regulate germ plasm assembly in the early embryo. We show that the Smaug (SMG) RBP is transported into the germ plasm of the early embryo where it accumulates in the germ granules. SMG binds to and represses translation of the osk messenger RNA (mRNA) as well as the bruno 1 ( bru1 ) mRNA, which encodes an RBP that we show promotes germ plasm production...
April 12, 2024: Science Advances
#17
JOURNAL ARTICLE
Kyung-Hee Kim, Eun Pyo Hong, Yukyeong Lee, Zachariah L McLean, Emanuela Elezi, Ramee Lee, Seung Kwak, Branduff McAllister, Thomas H Massey, Sergey Lobanov, Peter Holmans, Michael Orth, Marc Ciosi, Darren G Monckton, Jeffrey D Long, Diane Lucente, Vanessa C Wheeler, Marcy E MacDonald, James F Gusella, Jong-Min Lee
Many Mendelian disorders, such as Huntington's disease (HD) and spinocerebellar ataxias, arise from expansions of CAG trinucleotide repeats. Despite the clear genetic causes, additional genetic factors may influence the rate of those monogenic disorders. Notably, genome-wide association studies discovered somewhat expected modifiers, particularly mismatch repair genes involved in the CAG repeat instability, impacting age at onset of HD. Strikingly, FAN1 , previously unrelated to repeat instability, produced the strongest HD modification signals...
April 16, 2024: Proceedings of the National Academy of Sciences of the United States of America
#18
JOURNAL ARTICLE
Zhangli Zuo, Milena Edna Roux, Yasin F Dagdas, Eleazar Rodriguez, Morten Petersen
Evolutionarily conserved protein associated with topoisomerase II (PAT1) proteins activate mRNA decay through binding mRNA and recruiting decapping factors to optimize posttranscriptional reprogramming. Here, we generated multiple mutants of pat1, pat1 homolog 1 (path1), and pat1 homolog 2 (path2) and discovered that pat triple mutants exhibit extremely stunted growth and all mutants with pat1 exhibit leaf serration while mutants with pat1 and path1 display short petioles. All three PATs can be found localized to processing bodies and all PATs can target ASYMMETRIC LEAVES 2-LIKE 9 transcripts for decay to finely regulate apical hook and lateral root development...
April 11, 2024: FEBS Letters
#19
JOURNAL ARTICLE
Mariella Hurtado Silva, Ashley J van Waardenberg, Aya Mostafa, Susanne Schoch, Dirk Dietrich, Mark E Graham
To investigate the phosphorylation-based signaling and protein changes occurring early in epileptogenesis, the hippocampi of mice treated with pilocarpine were examined by quantitative mass spectrometry at 4 and 24 h post-status epilepticus at vast depth. Hundreds of posttranscriptional regulatory proteins were the major early targets of increased phosphorylation. At 24 h, many protein level changes were detected and the phosphoproteome continued to be perturbed. The major targets of decreased phosphorylation at 4 and 24 h were a subset of postsynaptic density scaffold proteins, ion channels, and neurotransmitter receptors...
April 19, 2024: IScience
#20
JOURNAL ARTICLE
Xiang-Ning Meng, Jin-Fa Ma, Yang-He Liu, Si-Qing Li, Xu Wang, Jing Zhu, Meng-Di Cai, Hui-Shu Zhang, Tiantian Song, Shukai Xing, Li-Qing Hou, Huan Guo, Xiao-Bo Cui, Jiang Han, Peng Liu, Guo-Hua Ji, Wen-Jing Sun, Jing-Cui Yu, Song-Bin Fu
BACKGROUND: Although DHFR gene amplification has long been known as a major mechanism for methotrexate (MTX) resistance in cancer, the early changes and detailed development of the resistance are not yet fully understood. METHODS: We performed genomic, transcriptional and proteomic analyses of human colon cancer cells with sequentially increasing levels of MTX-resistance. RESULTS: The genomic amplification evolved in three phases (pre-amplification, homogenously staining region (HSR) and extrachromosomal DNA (ecDNA))...
April 9, 2024: British Journal of Cancer
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