Review
Biochemistry & Molecular Biology
Patricia Martins-Dias, Luisa Romao
Summary: Nonsense mutations can lead to dysfunctional proteins, but nonsense suppression therapy has the potential to restore protein function and treat a variety of genetic disorders. However, the efficiency of suppression may be influenced by nonsense-mediated decay, highlighting the importance of using NMD inhibitors or readthrough-compound potentiators to enhance therapeutic effects.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Chemistry, Medicinal
Nesrine Benslimane, Federica Miressi, Camille Loret, Laurence Richard, Angelique Nizou, Ioanna Pyromali, Pierre-Antoine Faye, Frederic Favreau, Fabrice Lejeune, Anne-Sophie Lia
Summary: Nonsense mutations play a role in peripheral neuropathies by causing premature termination codons at the mRNA level. Readthrough molecules or NMD inhibitors, such as amlexanox, could be potential therapies for hereditary neuropathies. In the study, treatment with amlexanox on patient-derived neuronal cells carrying a specific mutation resulted in stabilization of GDAP1 mRNAs and restoration of mitochondrial morphology, highlighting the potential of readthrough molecules and NMD inhibitors for the treatment of genetic alterations in peripheral neuropathies.
Article
Biochemistry & Molecular Biology
Marta Vallverdu-Prats, Ramon Brugada, Mireia Alcalde
Summary: This study found that desmosomal genes carrying 5'-PTC can have different effects. Some genes trigger the NMD mechanism, leading to no gene expression, while others escape NMD through reinitiation of translation and produce N-truncated protein.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Federica Corrao, Maria Grazia Zizzo, Marco Tutone, Raffaella Melfi, Ignazio Fiduccia, Pietro Salvatore Carollo, Aldo Di Leonardo, Gaetano Caldara, Riccardo Perriera, Andrea Pace, Beatrice Belmonte, Selene Sammataro, Ivana Pibiri, Laura Lentini
Summary: This study investigated the acute toxicological effects of three Translational Readthrough Inducing Drugs (TRIDs) on mice and found that these drugs showed good tolerability without causing significant adverse effects in the mice.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Agathe Gilbert, Cosmin Saveanu
Summary: New findings challenge models for NMD mechanisms and suggest that the imbalance between active and inactive states of NMD complexes may contribute to RNA degradation defects.
Article
Pharmacology & Pharmacy
Renata B. V. Abreu, Thiago T. Gomes, Thales C. Nepomuceno, Xueli Li, Mateus Fuchshuber-Moraes, Giuliana De Gregoriis, Guilherme Suarez-Kurtz, Alvaro N. A. Monteiro, Marcelo A. Carvalho
Summary: This study evaluates the readthrough of clinically relevant PTC variants in the breast and ovarian cancer-predisposing gene BRCA1 for the first time, demonstrating that the aminoglycoside G418 can induce PTC readthrough and restore full-length protein synthesis and function.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Laure Bidou, Olivier Bugaud, Goulven Merer, Matthieu Coupet, Isabelle Hatin, Egor Chirkin, Sabrina Karri, Stephane Demais, Pauline Francois, Jean-Christophe Cintrat, Olivier Namy
Summary: In this study, a new drug was developed and evaluated for its clinical potential in treating genetic diseases caused by premature termination codons (PTCs). The drug, TLN468, was found to be more effective than the currently used gentamicin and acted on a broader range of sequences without affecting normal stop codon readthrough.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Yanwu Guo, Cristina Tocchini, Rafal Ciosk
Summary: This study identified a conserved gene clk-2 as a key player in nematode NMD pathway, while its human counterpart TELO2 is also implicated in NMD. Variants in TELO2 have been linked to an intellectual disability disorder, suggesting a potential role in the NMD pathway.
Article
Biochemistry & Molecular Biology
Daniel R. McHugh, Calvin U. Cotton, Craig A. Hodges
Summary: This study demonstrated synergy between NMD inhibitors and readthrough agents in increasing functional protein quantity following readthrough, suggesting a potential therapeutic option for treating nonsense mutations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Caleb M. Embree, Rabab Abu-Alhasan, Guramrit Singh
Summary: Nonsense-mediated mRNA decay is a quality control pathway that prevents the production of truncated polypeptides and regulates gene expression. It is closely linked to translation termination, and abnormal termination can trigger events that destabilize mRNA. Understanding the mechanisms and escape pathways of NMD is crucial for human health.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Hana Cho, Elizabeth T. Abshire, Maximilian W. Popp, Christoph Proschel, Joshua L. Schwartz, Gene W. Yeo, Lynne E. Maquat
Summary: This study identifies 13 proteins constituting the AKT signaling pathway as novel effectors of nonsense-mediated mRNA decay (NMD). The study shows that AKT supersedes UPF2 in exon-junction complexes (EJCs) and increases UPF1 helicase activity through phosphorylation, contributing to the hyperactivation of NMD in Fragile X syndrome.
Article
Biochemistry & Molecular Biology
Venkateshwar Mutyam, Jyoti Sharma, Yao Li, Ning Peng, Jianguo Chen, Li Ping Tang, Emily Falk Libby, Ashvani K. Singh, Katja Conrath, Steven M. Rowe
Summary: Premature-termination codons (PTCs) in the CFTR gene lead to nonfunctional CFTR protein, accounting for 11% of CF-causing alleles with no current effective treatments. Novel CFTR correctors and potentiators show comparable effects to existing ones in vitro, and their combination can enhance the improvement of CFTR function with terminal PTC mutations.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Hanae Sato, Robert H. Singer
Summary: The author developed a single-cell reporter system to investigate cell-to-cell variability of NMD efficiency. The study revealed a wide range of NMD efficiency in different cells, potentially linked to the expression levels of surveillance factors.
NATURE COMMUNICATIONS
(2021)
Article
Biology
Yukio Kurihara, Yuko Makita, Masaharu Kawauchi, Ami Kageyama, Tomoko Kuriyama, Minami Matsui
Summary: Recent evidence suggests the existence of readthrough transcripts (RTs), including polycistronic mRNAs, in eukaryotes. This study identifies 271 loci producing polycistronic RTs in Arabidopsis. The accumulation of RTs is increased in NMD-deficient mutants compared to the wild type. Additionally, the translation of the second open reading frames (ORFs) of bicistronic mRNAs is rare. Intergenic splicing (IS) events occur in 158 RTs, and inhibiting splicing promotes the accumulation of RTs.
COMMUNICATIONS BIOLOGY
(2022)
Article
Genetics & Heredity
Kai Yan, Yixi Sun, Yanmei Yang, Bei Liu, Minyue Dong
Summary: This study identified a missense mutation affecting the splicing process, which was located at a non-canonical splicing site. The pathogenicity of the mutation was confirmed through experimental validation, and it expanded the spectrum of pathogenic mutations in Bardet-Biedl syndrome type I.
FRONTIERS IN GENETICS
(2022)
Article
Genetics & Heredity
Xiangge Meng, Chengping Li, Yu Hei, Xiang Zhou, Guoli Zhou
Summary: The study used IVT-SAPAS sequencing to analyze the dynamic changes of APA sites during adipogenesis in bovine subcutaneous preadipocytes and intramuscular preadipocytes. The results showed that APA plays an important role in adipocyte differentiation, and UTR-APA switching genes have different trends, with intramuscular preadipocytes tending to use shorter 3'UTR for differentiation. TRIB3, WWTR1, and INSIG1 play important roles in intramuscular preadipocyte differentiation.
Article
Genetics & Heredity
S. Alizadeh, S. Khamse, N. Tajeddin, H. R. Khorram Khorshid, A. Delbari, M. Ohadi
Summary: This study identifies a specific genotype at a CG-rich trinucleotide short tandem repeat (STR) locus that is associated with late-onset neurocognitive disorders such as Alzheimer's disease (AD).
Article
Genetics & Heredity
Shougang Liu, Zhe Zhuang, Fanghua Liu, Xiuqing Yuan, Zeqiao Zhang, Xiaoqian Liang, Xinhui Li, Yongfeng Chen
Summary: This study investigated the effect and mechanism of RPL9 and TIFA in scalp psoriasis, and identified RPL9 as a potential therapeutic target for scalp psoriasis.
Article
Genetics & Heredity
Shiting Wang, Jiaqi Chen, Zhichao Jin, Ying Xing, Ruiping Wang
Summary: This study suggests a causal association between hair color and skin cancers, with light hair colors (red, blonde, and light brown) being associated with an increased risk and dark brown hair being associated with a decreased risk.
Article
Genetics & Heredity
Joseph Hawadak, Loick Pradel Kojom Foko, Rodrigue Roman Dongang Nana, Karmveer Yadav, Veena Pande, Aparup Das, Vineeta Singh
Summary: This study investigates the genetic diversity and natural selection of the Pfama-1 gene in Plasmodium falciparum isolates from Cameroon. The study finds a considerable nucleotide and haplotype diversity, as well as specific mutations in Cameroonian isolates. Positive diversifying selection and the identification of selected codon sites suggest the potential implication of these genetic variations in host immune pressure and parasite-binding complex modulation. The findings provide valuable baseline data for malaria vaccine design.
Article
Genetics & Heredity
Emily Biernat, Mansi Verma, Chhabi K. Govind
Summary: RSC is an essential ATP-dependent chromatin remodeling complex in Saccharomyces cerevisiae. It regulates nucleosome-depleted regions (NDRs) by sliding flanking nucleosomes away from NDRs. Depletion of RSC leads to nucleosome encroachment in NDRs and transcription initiation defects. The study compared the effects of catalytic-dead Sth1 and rapid depletion of Sth1 on transcription. Rapid depletion of Sth1 reduces recruitment of TBP and Pol II, while the catalytic-dead mutant exhibits a severe reduction in TBP binding but accumulates Pol II in coding regions. The results suggest a role for RSC in transcription elongation and termination processes.
Article
Genetics & Heredity
Yunxiao Wei, Yuhan Song, Muhammad Aamir Khan, Chengzhen Liang, Zhigang Meng, Yuan Wang, Sandui Guo, Rui Zhang
Summary: This study analyzed the GhTPP protein family in upland cotton for the first time and identified the important role of GhTPPA_2 in regulating sugar metabolism, improving soluble sugar accumulation, and drought stress tolerance.
Article
Genetics & Heredity
Yannan Geng, Rui Shao, Tiantong Xu, Lilong Zhang
Summary: A novel risk model based on SCUBE3, TNNC1, SPON1, SEPT12 and ULBP1 genes was developed for predicting PMOP risk, with higher risk score indicating higher risk of suffering from PMOP. Significant differences in signaling pathway activities were observed between the high-risk score group and the low-risk score group.
Article
Genetics & Heredity
Randy P. Williams, Corina Lesseur, Haoxiang Cheng, Qian Li, Maya Deyssenroth, Christopher D. Molteno, Ernesta M. Meintjes, Sandra W. Jacobson, Joseph L. Jacobson, Helen Wainwright, Ke Hao, Jia Chen, R. Colin Carter
Summary: The study suggests that heavy alcohol exposure during pregnancy may impact the proportion of fetal placental villi macrophages and increase the expression of inflammatory genes. Further research is needed to explore these effects and evaluate the potential functional roles of placental inflammation in FASD.
Article
Genetics & Heredity
Lvjing Luo, Lishuang Sun, Shu Li, Huiting Liu, Zhengyu Chen, Shi Huang, Yinyin Mo, Genliang Li
Summary: This study analyzed the expression of Ptpn1 and miR-124-3p in testicular tissues of mice and investigated their regulatory relationship. The results showed that Ptpn1 expression was up-regulated in adult mouse testis compared to juvenile mouse testis, while miR-124-3p expression showed an opposite pattern. Further analysis suggested that the down-regulation of miR-124-3p may contribute to the high expression of Ptpn1 in adult mouse testis.
Article
Genetics & Heredity
Gairui Li, Dan Zhao, Xiaolin Peng, Yashuang Zhao
Summary: MiRNA-22 shows potential as a candidate for early diagnosis of colorectal cancer (CRC). The study found higher miR-22 expression levels in the CRC and CRA groups, suggesting its potential as a biomarker for CRC early screening.
Article
Genetics & Heredity
Zhongqiu Zhu, Qianting Yang, Xiaoying Tian, Da Man, Jian Wang, Junfang Zhang, Bingshe Han
Summary: This study constructed a ceRNA network mediated by lncRNAs in cold-acclimated zebrafish ZF4 cells and revealed that upregulation of MSTRG3207 promotes apoptosis by sponging dre-miR-736 during cold acclimation.
Article
Genetics & Heredity
Weitao Chen, Denggao Xiang, Shang Gao, Shuli Zhu, Zhi Wu, Yuefei Li, Jie Li
Summary: Dam construction has negatively impacted the genetic diversity and structure of fish populations. This case study on the endangered Hemibagrus guttatus found low genetic diversity, high levels of inbreeding, and decreasing population size in fragmented populations. Genetic structure and differentiation were also observed, indicating the influence of dams on these fish populations.
Article
Genetics & Heredity
Pooja Singh, Debleena Guin, Bijay Pattnaik, Ritushree Kukreti
Summary: Through systematic literature review and meta-analysis, it was found that idiopathic pulmonary fibrosis is significantly associated with 222 polymorphisms in 118 genes. Four polymorphisms - rs35705950/MUC5B, rs2736100/TERT, rs2076295/DSP, and rs111521887/TOLLIP, exhibited substantial epidemiological evidence supporting their association with IPF risk.
Article
Genetics & Heredity
Jianping Zhang, Zhijun Cai, Fanzhe Feng, Yufeng Peng, Yi Cui, Yongiqing Xu
Summary: This study found that exosomes secreted by young BMSCs can promote the healing of tendon-bone interface after rotator cuff tears. These exosomes can improve extracellular matrix remodeling, osteogenic differentiation, angiogenesis, and stemness of tendon-derived stem cells (TDSCs). The exosomes from young BMSCs have better effects compared to those from aged BMSCs.