Article
Biochemistry & Molecular Biology
Sven Vanselow, Lea Neumann-Arnold, Franziska Wojciech-Moock, Wolfgang Seufert
Summary: This study reveals the assembly mechanism and individual functions of different subunits of the eukaryotic translation initiation factor 2 (eIF2). The research shows that a conformational change in the eIF2 gamma subunit, mediated by Cdc123, exposes binding sites for eIF2 alpha and eIF2 beta subunits. Contrary to previous hypotheses, the associations between eIF2 alpha and eIF2 beta with the gamma subunit are independent of each other. Furthermore, the resulting heterodimers are nonfunctional and fail to bind the guanosine exchange factor eIF2B. This study provides insights into an essential step in translation initiation, with implications for understanding human diseases related to dysfunction in this process.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Genetics & Heredity
Ryszard Slezak, Robert Smigiel, Ewa Obersztyn, Agnieszka Pollak, Mateusz Dawidziuk, Wojciech Wiszniewski, Monika Bekiesinska-Figatowska, Malgorzata Rydzanicz, Rafal Ploski, Pawel Gawlinski
Summary: This article describes three new cases of MCPH2 with compound heterozygous mutations in the WDR62 gene, all presenting similar clinical features. Other gene variants were also found in some cases, with unknown effects on disease progression. Additionally, the study collected and compared common clinical symptoms, dysmorphic features, and brain radiographic changes in 120 patients with recessive primary microcephaly type 2 caused by mutations in the WDR62 gene.
Article
Biochemistry & Molecular Biology
Patrick Senechal, Francis Robert, Regina Cencic, Akiko Yanagiya, Jennifer Chu, Nahum Sonenberg, Marilene Paquet, Jerry Pelletier
Summary: The translation initiation factor eIF4F is crucial for cap-dependent protein synthesis initiation. Different subunits of eIF4F have varying roles in development and tumorigenesis, with some being essential for viability and tumor onset, while others have non-essential functions. This study highlights the complex roles of different eIF4F subunits in gene expression regulation during embryogenesis and tumor development.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Endocrinology & Metabolism
Maddalena Petraroli, Antonio Percesepe, Maria Piane, Francesca Ormitti, Eleonora Castellone, Margherita Gnocchi, Giulia Messina, Luca Bernardi, Viviana Dora Patianna, Susanna Maria Roberta Esposito, Maria Elisabeth Street
Summary: We report the case of a 3-year-old boy with severe growth failure, intellectual disability, microcephaly, skeletal anomalies, and kidney and liver abnormalities. Genetic analysis revealed a novel homozygous pathogenic variant in the PCNT gene. The boy died at 8 years of age due to intracranial hemorrhage associated with Moyamoya malformation. Early detection of intracranial and kidney anomalies is crucial for the management of patients with microcephalic osteodysplastic primordial dwarfism type II (MOPDII).
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Genetics & Heredity
Cosima M. Schmid, Anne Gregor, Gregory Costain, Chantal F. Morel, Lauren Massingham, Jennifer Schwab, Chloe Quelin, Marie Faoucher, Julie Kaplan, Rebecca Procopio, Carol J. Saunders, Ana S. A. Cohen, Gabrielle Lemire, Stephanie Sacharow, Anne O'Donnell-Luria, Ranit Jaron Segal, Jessica Kianmahd Shamshoni, Daniela Schweitzer, Darius Ebrahimi-Fakhari, Kristin Monaghan, Timothy Blake Palculict, Melanie P. Napier, Alice Tao, Bertrand Isidor, Kamran Moradkhani, Andre Reis, Heinrich Sticht, Wendy K. Chung, Christiane Zweier
Summary: Through international collaboration, we identified individuals carrying small chromosomal deletions, gene-disrupting or missense variants in LHX2, and they presented with neurodevelopmental phenotypes. Our findings implicate LHX2 haploinsufficiency as causative for neurodevelopmental disorders.
GENETICS IN MEDICINE
(2023)
Review
Genetics & Heredity
Prakash Amruth Raj Chukka, Stacey D. Wetmore, Nehal Thakor
Summary: Translational control plays a crucial role in dictating gene expression and altering physiological processes in eukaryotic cells. eIF5B plays a significant role in this process, especially in the survival and drug resistance of cancer cells.
FRONTIERS IN GENETICS
(2021)
Article
Clinical Neurology
Aysan Moeinafshar, Sahand Tehrani Fateh, Hossein Sadeghi, Parvaneh Karimzadeh, Reza Mirfakhraie, Farzad Hashemi-Gorji, Pegah Larki, Mohammad Miryounesi, Mohammad-Reza Ghasemi
Summary: Neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV) is a rare autosomal dominant genetic disorder caused by genetic alterations in the CTNNB1 gene. This study reports two cases of NEDSDV with de novo CTNNB1 mutations and describes their clinical and paraclinical characteristics. Identification of new patients and novel variants is important for establishing a more complete phenotypic spectrum and genotype-phenotype correlations in these cases.
NEUROLOGICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Paul Powell, Usha Bhardwaj, Dixie Goss
Summary: This study identifies secondary structures that selectively interact with eIF3 and explores its role in translation initiation of BYDV. The findings propose a new model for BYDV translation initiation and expand the known functionality of eIF3.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Daniel Friedrich, Assen Marintchev, Haribabu Arthanari
Summary: In this review, the authors examine the versatility and functionality of HEAT domains in the regulation of mRNA translation initiation. They describe the basic structural architecture of HEAT domains and their involvement in various cellular processes. The focus is on proteins in the translation initiation system that feature HEAT domains, highlighting their remarkably flexible interactions and the functional importance of these domains.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Oncology
Chengzhi Xu, Yupeng Shen, Yong Shi, Ming Zhang, Liang Zhou
Summary: This study reveals the role of EIF3B in head and neck squamous cell carcinoma (HNSCC) and identifies its promotion of CEBPB translation and IL6R expression. These findings provide important insights into the molecular basis and pathogenesis of HNSCC.
CANCER CELL INTERNATIONAL
(2022)
Review
Biochemistry & Molecular Biology
Jerry Pelletier, Nahum Sonenberg
Summary: Fundamental studies have elucidated the role of eukaryotic initiation factor (eIF) 4E in mRNA translation and its regulation. The regulation of translation by eIF4E is crucial for cellular homeostasis under normal conditions. In response to stress, eIF4E processes gene flow information to support adaptive mechanisms for cell survival. Dysregulated eIF4E activity contributes to tumor development, progression, and therapy response modulation. Therefore, there is a growing interest in understanding eIF4E function in gene expression control and developing strategies to inhibit its activity for disease treatment.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2023)
Article
Biochemistry & Molecular Biology
Su Wu, Gerhard Wagner
Summary: eIF4F plays diverse roles in human cancers, with overexpression of EIF4G1 being more selective than EIF4E, serving as a prognostic indicator in cancer patients. This expression imbalance affects housekeeping pathways and cancer-related pathways, leading to cap-independent initiation due to eIF4G1 hyperphosphorylation. These findings provide a novel model of dysregulated eIF4F function and highlight the clinical relevance of cap-(in)dependent initiation in cancer.
Review
Cell Biology
Yudi Liu, Jiuwei Cui, Andrew R. Hoffman, Ji-Fan Hu
Summary: Protein translation is a critical regulatory event involved in various physiological and pathological processes. The eukaryotic translation initiation factor 4G2 (eIF4G2) is important for cap-independent translation initiation via internal ribosome entry sites (IRESs), but recent findings suggest that it plays a role in other translation initiation pathways as well. This review summarizes the role of eIF4G2 in different translation initiation events and its involvement in apoptosis, cell survival, cell differentiation, and embryonic development.
CELL PROLIFERATION
(2023)
Article
Biochemistry & Molecular Biology
Xiaozhuo Liu, Houtan Moshiri, Qian He, Ansuman Sahoo, Sarah E. Walker
Summary: The yeast eukaryotic initiation factor 4B plays an important role in translation preinitiation complexes. Recent studies have found that yeast mRNAs have differential dependence on eIF4B under different growth conditions. It is suggested that the activity of eIF4B in translation may alter yeast phenotypes by selecting different mRNAs. By comparing the effects of disrupting yeast eIF4B RNA- and 40S-binding motifs, it is found that the 40S-binding N-terminal Domain (NTD) is associated with stress responses and promotes yeast growth. Deletion of the NTD significantly reduces translation activity and alters the composition of ribosome-associated mRNAs. Gene ontology analysis reveals that transcripts dependent on the NTD encode proteins associated with the cellular membrane system and the cell wall.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Developmental Biology
Yan Li, Jianan Tang, Xu Ji, Min-Min Hua, Miao Liu, Lu Chang, Yihua Gu, Changgen Shi, Wuhua Ni, Jing Liu, Hui-juan Shi, Xuefeng Huang, Christopher O'Neill, Xingliang Jin
Summary: The translation initiation factor eIF4E plays a crucial role in cap-dependent translation and the transition from maternal to embryonic control of mouse embryo development. Inhibiting eIF4E activity leads to developmental arrest at the two-cell stage, highlighting the importance of eIF4E in early embryonic transitions. This study also shows that mTOR activity and the negative regulator 4E-BP1 are involved in regulating eIF4E activity during embryonic development.
Article
Biochemistry & Molecular Biology
Jason R. Vanstone, Amanda M. Smith, Skye McBride, Turaya Naas, Martin Holcik, Ghadi Antoun, Mary-Ellen Harper, Jean Michaud, Erick Sell, Pranesh Chakraborty, Martine Tetreault, Jacek Majewski, Stephen Baird, Kym M. Boycott, David A. Dyment, Alex MacKenzie, Matthew A. Lines
EUROPEAN JOURNAL OF HUMAN GENETICS
(2016)
Article
Biochemistry & Molecular Biology
Nehal Thakor, M. Duane Smith, Luc Roberts, Mame Daro Faye, Harshil Patel, Hans-Joachim Wieden, Jamie H. D. Cate, Martin Holcik
Article
Oncology
Christine C. Dobson, Thet Naing, Shawn T. Beug, Mame D. Faye, Janelle Chabot, Martin St-Jean, Danielle E. Walker, Eric C. LaCasse, David F. Stojdl, Robert G. Korneluk, Martin Holcik
Article
Multidisciplinary Sciences
Bahram Samanfar, Kristina Shostak, Houman Moteshareie, Maryam Hajikarimlou, Sarah Shaikho, Katayoun Omidi, Mohsen Hooshyar, Daniel Burnside, Imelda Galvan Marquez, Tom Kazmirchuk, Thet Naing, Paula Ludovico, Anna York-Lyon, Kama Szereszewski, Cindy Leung, Jennifer Yixin Jin, Rami Megarbane, Myron L. Smith, Mohan Babu, Martin Holcik, Ashkan Golshani
Article
Psychology, Biological
Gary S. Goldfield, Glen P. Kenny, Denis Prud'homme, Martin Holcik, Angela S. Alberga, Margaret Fahnestock, Jameason D. Cameron, Steve Doucette, Stasia Hadjiyannakis, Heather Tulloch, Mark S. Tremblay, Jeremy Walsh, Eva Guerin, Katie E. Gunnell, Amedeo D'Angiulli, Ronald J. Sigal
PHYSIOLOGY & BEHAVIOR
(2018)
Correction
Psychology, Biological
Gary S. Goldfield, Glen P. Kenny, Denis Prud'homme, Martin Holcik, Angela S. Alberga, Margaret Fahnestock, Jameason D. Cameron, Steve Doucette, Stasia Hadjiyannakis, Heather Tulloch, Mark S. Tremblay, Jeremy Walsh, Eva Guerin, Katie E. Gunnell, Amedeo D'Angiulli, Ronald J. Sigal
PHYSIOLOGY & BEHAVIOR
(2019)
Article
Multidisciplinary Sciences
Houman Moteshareie, Maryam Hajikarimlou, Alex Mulet Indrayanti, Daniel Burnside, Ana Paula Dias, Clara Lettl, Duale Ahmed, Katayoun Omidi, Tom Kazmirchuk, Nathalie Puchacz, Narges Zare, Sarah Takallou, Thet Naing, Raul Bonne Hernandez, William G. Willmore, Mohan Babu, Bruce McKay, Bahram Samanfar, Martin Holcik, Ashkan Golshani
Article
Neurosciences
Jeremy J. Walsh, Amedeo D'Angiulli, Jameason D. Cameron, Ronald J. Sigal, Glen P. Kenny, Martin Holcik, Steve Doucette, Angela S. Alberga, Denis Prud'homme, Stasia Hadjiyannakis, Katie Gunnell, Gary S. Goldfield
Article
Biochemistry & Molecular Biology
Golnoush Hassanzadeh, Thet Naing, Tyson Graber, Seyed Mehdi Jafarnejad, David F. Stojdl, Tommy Alain, Martin Holcik
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Review
Biochemistry & Molecular Biology
Angelo Slade, Ribal Kattini, Chloe Campbell, Martin Holcik
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Maryam Hajikarimlou, Kathryn Hunt, Grace Kirby, Sarah Takallou, Sasi Kumar Jagadeesan, Katayoun Omidi, Mohsen Hooshyar, Daniel Burnside, Houman Moteshareie, Mohan Babu, Myron Smith, Martin Holcik, Bahram Samanfar, Ashkan Golshani
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Krishna Bhattarai, Travis Richard, Thet Fatica, Brianna Frangione, William G. Willmore, Martin Holcik
Summary: hnRNP A1 is an important nucleocytoplasmic-shuttling RNA-binding protein that plays a role in nucleic acid metabolism and gene expression regulation. Our study reveals that the kinase ARK5 interacts with and phosphorylates hnRNP A1, controlling its subcellular localization during hypertonic stress.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Multidisciplinary Sciences
Ammanie Abdul-Fatah, Leila Esmaeilisaraji, Crisel Mae Juan, Martin Holcik
Summary: This paper provides support for the creation of a mitochondrial disease patient registry in Canada through a systematic scoping review. It also fills a knowledge gap by providing a narrative synthesis of published literature on these registries.
Article
Genetics & Heredity
Thet Fatica, Turaya Naas, Urszula Liwak, Hannah Slaa, Maryam Souaid, Brianna Frangione, Ribal Kattini, Antoine Gaudreau-Lapierre, Laura Trinkle-Mulcahy, Pranesh Chakraborty, Martin Holcik
Summary: Mitochondrial diseases are caused by dysfunctional mitochondria, and a significant portion of these diseases are associated with defects in genes responsible for tRNA metabolism. Partial loss-of-function mutations in the TRNT1 gene, which encodes the CCA-adding enzyme essential for modifying both nuclear and mitochondrial tRNAs, lead to a clinically heterogeneous disease called SIFD. Studies have found that TRNT1 deficiency results in increased sensitivity to oxidative stress and dysregulation of tRNA maturation and abundance, ultimately affecting the translation of specific proteins.
Article
Microbiology
Maryam Hajikarimlou, Mohsen Hooshyar, Noor Sunba, Nazila Nazemof, Mohamed Taha Moutaoufik, Sadhena Phanse, Kamaledin B. B. Said, Mohan Babu, Martin Holcik, Bahram Samanfar, Myron Smith, Ashkan Golshani
Summary: Mitochondria possess their own DNA (mtDNA) and are capable of carrying out their transcription and translation. The presence of the 3'-UTR from OXA1 gene is correlated with mitochondrial translation in yeast.