Article
Biology
Sven Dennerlein, Sabine Poerschke, Silke Oeljeklaus, Cong Wang, Ricarda Richter-Dennerlein, Johannes Sattmann, Diana Bauermeister, Elisa Hanitsch, Stefan Stoldt, Thomas Langer, Stefan Jakobs, Bettina Warscheid, Peter Rehling
Summary: TMEM223 and SMIM4 were identified as ribosome-associated proteins involved in complex IV and III biogenesis, respectively. They stimulate mRNA translation and support early assembly steps, linking translation machinery to the biogenesis of OXPHOS complexes.
Article
Biology
Shu Zhang, Chang Wang, Yue Wang, Hao Zhang, Chen Xu, Yiwei Cheng, Yan Yuan, Jiahao Sha, Xuejiang Guo, Yiqiang Cui
Summary: In this study, an endogenous circular RNA (circRsrc1) was discovered, which encodes a novel protein (Rsrc1-161aa). Deletion of Rsrc1-161aa in mice resulted in impaired male fertility, characterized by decreased sperm count and motility due to mitochondrial energy metabolism dysfunctions. In vitro experiments showed that circRsrc1 regulates mitochondrial functions through its encoded protein Rsrc1-161aa. Mechanistically, Rsrc1-161aa interacts with mitochondrial protein C1qbp to enhance its binding activity to mitochondrial mRNAs, thereby regulating mitochondrial ribosome assembly and translation.
Article
Multidisciplinary Sciences
Aleksandar Radakovic, Saurja DasGupta, Tom H. Wright, Harry R. M. Aitken, Jack W. Szostak
Summary: Research shows that aminoacylated RNAs can assemble into chimeric amino acid-RNA polymers with active ribozyme function under template guidance, potentially introducing new functionalities in ribozyme catalysis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Kah Ying Ng, Guleycan Lutfullahoglu Bal, Uwe Richter, Omid Safronov, Lars Paulin, Cory D. Dunn, Ville O. Paavilainen, Julie Richer, William G. Newman, Robert W. Taylor, Brendan J. Battersby
Summary: Translation termination in protein synthesis is facilitated by a stop codon within mRNA. However, transcripts lacking a stop codon can lead to nonstop ribosome complexes. In this study, deep sequencing was used to investigate nonstop mRNAs generated from the human mitochondrial genome. Various types of nonstop mRNAs resistant to translation termination by canonical release factors were identified. The failure to resolve these aberrations by the mitochondrial release factor can negatively regulate protein synthesis and be associated with human disease.
Article
Biochemistry & Molecular Biology
Xiongwen Cao, Alexandra Khitun, Cecelia M. Harold, Carson J. Bryant, Shu-Jian Zheng, Susan J. Baserga, Sarah A. Slavoff
Summary: This study discovered unannotated alt-proteins that play important roles in DNA damage stress and cell cycle regulation. One of these alt-proteins, MINAS-60, was found to negatively regulate assembly of the pre-60S ribosomal subunit. Depletion of MINAS-60 increases cytoplasmic 60S ribosomal subunit, leading to upregulated protein synthesis and cell proliferation.
NATURE CHEMICAL BIOLOGY
(2022)
Review
Cell Biology
Fei Wang, Deyu Zhang, Dejiu Zhang, Peifeng Li, Yanyan Gao
Summary: Mitochondria in cells are crucial organelles with their own genetic system, and their protein translation process is regulated by various factors that, when abnormal, can lead to diseases. The balance between mitochondrial protein translation and cytoplasmic translation is also important for physiological and pathological processes in the body.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biology
Soichiro Hoshino, Ryohei Kanemura, Daisuke Kurita, Yukihiro Soutome, Hyouta Himeno, Masak Takaine, Masakatsu Watanabe, Nobukazu Nameki
Summary: The study demonstrates that the S. cerevisiae homolog of C12orf65, Pth3, is essential for the translation of mitochondrial genes in the presence of antibiotics. Pth3 is shown to rescue ribosomes stalled by antibiotics, contributing to antibiotic resistance in fungi.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Soma Jana, Partha P. Datta
Summary: The study found that the pI values of translation factors are related to the translation event, where initiation factors are mainly basic, while elongation and release factors are strictly acidic. Among all translation factors, initiation factor 2 (IF2) and ribosome recycling factor (RRF) showed variable pI values that are linked to the order of phylogeny.
Article
Multidisciplinary Sciences
Yuzuru Itoh, Anas Khawaja, Ivan Laptev, Miriam Cipullo, Ilian Atanassov, Petr Sergiev, Joanna Rorbach, Alexey Amunts
Summary: This study reveals the sequential assembly mechanism of the small mitoribosomal subunit (SSU) using cryo-electron microscopy. The results demonstrate the role of auxiliary factors in promoting rRNA maturation and conformational changes, leading to the formation of the catalytic human mitoribosome.
Article
Biochemical Research Methods
Artyom A. Egorov, Gemma C. Atkinson
Summary: This article presents a tool for annotating conserved uORFs, which can predict functional ORFs in the upstream sequences of a user-defined protein or a set of protein homologs. It generates publication-quality figures with multiple sequence alignments, sequence logos, and locus annotation of the predicted conserved uORFs in graphical vector format.
Article
Biochemistry & Molecular Biology
Victor Tobiasson, Ondrej Gahura, Shintaro Aibara, Rozbeh Baradaran, Alena Zikova, Alexey Amunts
Summary: This study identified key factors involved in the assembly of the mitoribosomal large subunit and revealed their functions. An extensive network of accessory factors stabilizes immature sites and connects functionally important regions of the mitoribosomal large subunit.
Article
Multidisciplinary Sciences
Yan Zhang, Nikolay A. Aleksashin, Dorota Klepacki, Caleb Anderson, Nora Vazquez-Laslop, Carol A. Gross, Alexander S. Mankin
Summary: Kasugamycin (KSG) is a small ribosomal subunit-targeting antibiotic that interferes with translation in different stages. It inhibits protein synthesis by blocking the binding of canonical messenger RNA (mRNA) and initiator transfer RNA (tRNA) to the small ribosomal subunit. Even after the formation of the 70S initiation complex, KSG can still interfere with translation to a certain extent. However, it does not completely abolish translation and allows for the expression of certain proteins. The effectiveness of KSG depends on the nature of the mRNA residue preceding the start codon and is attenuated by translational coupling.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Gillian Rexroad, John Paul Donohue, Laura Lancaster, Harry F. Noller
Summary: This study investigates the impact of GTP hydrolysis inhibition on the structural dynamics of the ribosome using ensemble FRET. The results show that blocking GTP hydrolysis slows both forward and reverse head rotation, and abolishes reverse head rotation. The study also reveals that the FRET pair used to monitor head rotation mainly reports on intersubunit rotation, and the signal from mRNA quenching correlates closely with reverse intersubunit rotation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Marjolein M. J. Caron, Maxime Eveque, Berta Cillero-Pastor, Ron M. A. Heeren, Bas Housmans, Kasper Derks, Andy Cremers, Mandy J. Peffers, Lodewijk W. van Rhijn, Guus van den Akker, Tim J. M. Welting
Summary: Sox9 plays an essential role in regulating ribosome biogenesis factors and ribosomal protein subunits during the early phase of chondrogenic differentiation, affecting translational capacity. Sox9 knockdown leads to decreased translation activity, while overexpression of Sox9 induces reciprocal effects.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biology
Swati Gaikwad, Fardin Ghobakhlou, David J. Young, Jyothsna Visweswaraiah, Hongen Zhang, Alan G. Hinnebusch
Summary: The formation of the 43S preinitiation complex is a critical step in translation in eukaryotes. Studies show that when there is a limitation in 43S PIC assembly, strong mRNAs outcompete weak mRNAs during translation, leading to a reprograming in translational efficiencies.
Article
Medicine, Research & Experimental
Romina Durigon, Alice L. Mitchell, Aleck W. E. Jones, Andreea Manole, Mara Mennuni, Elizabeth M. A. Hirst, Henry Houlden, Giuseppe Maragni, Serena Lattante, Paolo Niccolo' Doronzio, Ilaria Dalla Rosa, Marcella Zollino, Ian J. Holt, Antonella Spinazzola
EMBO MOLECULAR MEDICINE
(2018)
Meeting Abstract
Clinical Neurology
E. Bugiardini, A. Mitchell, I. Dalla Rosa, M. Menunni, A. Pittmann, O. Poole, J. Holton, R. Quinlivan, I. Holt, H. Houlden, M. G. Hanna, A. Spinazzola, R. D. S. Pitceathly
NEUROMUSCULAR DISORDERS
(2018)
Article
Biochemistry & Molecular Biology
Tricia J. Cluett, Gokhan Akman, Aurelio Reyes, Lawrence Kazak, Alice Mitchell, Stuart R. Wood, Antonella Spinazzola, Johannes N. Spelbrink, Ian J. Holt
NUCLEIC ACIDS RESEARCH
(2018)
Article
Multidisciplinary Sciences
S. A. Baechler, V. M. Factor, I Dalla Rosa, A. Ravji, D. Becker, S. Khiati, L. M. Miller Jenkins, M. Lang, C. Sourbier, S. A. Michaels, L. M. Neckers, H. L. Zhang, A. Spinazzola, S. N. Huang, J. U. Marquardt, Y. Pommier
NATURE COMMUNICATIONS
(2019)
Article
Biochemistry & Molecular Biology
Enrico Bugiardini, Alice L. Mitchell, Ilaria Dalla Rosa, Hue-Tran Horning-Do, Alan M. Pitmann, Olivia Poole, Janice L. Holton, Sachit Shah, Cathy Woodward, Iain Hargreaves, Rosaline Quinlivan, Alexey Amunts, Rudolf J. Wiesner, Henry Houlden, Ian J. Holt, Michael G. Hanna, Robert D. S. Pitceathly, Antonella Spinazzola
HUMAN MOLECULAR GENETICS
(2019)
Review
Cell Biology
Simone A. Baechler, Ilaria Dalla Rosa, Antonella Spinazzola, Yves Pommier
Article
Clinical Neurology
Beatriz De la Casa-Fages, Gorka Fernandez-Eulate, Josep Gamez, Raul Barahona-Hernando, German Moris, Maria Garcia-Barcina, Jon Infante, Miren Zulaica, Uxoa Fernandez-Pelayo, Mikel Munoz-Oreja, Miguel Urtasun, Ander Olaskoaga, Victoria Zelaya, Ivonne Jerico, Raquel Saez-Villaverde, Irene Catalina, Emma Sola, Elena Martinez-Saez, Aurora Pujol, Montserrat Ruiz, Agatha Schluter, Antonella Spinazzola, Jose Luis Munoz-Blanco, Francisco Grandas, Ian Holt, Victoria Alvarez, Adolfo Lopez de Munain
MOVEMENT DISORDERS
(2019)
Article
Genetics & Heredity
Ewen W. Sommerville, Ilaria Dalla Rosa, Masha M. Rosenberg, Francesco Bruni, Kyle Thompson, Mariana Rocha, Emma L. Blakely, Langping He, Gavin Falkous, Andrew M. Schaefer, Patrick Yu-Wai-Man, Patrick F. Chinnery, Lizbeth Hedstrom, Antonella Spinazzola, Robert W. Taylor, Grainne S. Gorman
Article
Genetics & Heredity
Adam C. Gunning, Klaudia Strucinska, Mikel Munoz Oreja, Andrew Parrish, Richard Caswell, Karen L. Stals, Romina Durigon, Karina Durlacher-Betzer, Mitchell H. Cunningham, Christopher M. Grochowski, Julia Baptista, Carolyn Tysoe, Emma Baple, Nayana Lahiri, Tessa Homfray, Ingrid Scurr, Catherine Armstrong, John Dean, Uxoa Fernandez Pelayo, Aleck W. E. Jones, Robert W. Taylor, Vinod K. Misra, Wan Hee Yoon, Caroline F. Wright, James R. Lupski, Antonella Spinazzola, Tamar Harel, Ian J. Holt, Sian Ellard
AMERICAN JOURNAL OF HUMAN GENETICS
(2020)
Letter
Clinical Neurology
Beatriz De la Casa-Fages, Gorka Fernandez-Eulate, Josep Gamez, Raul Barahona-Hernando, German Moris, Maria Garcia-Barcina, Jon Infante, Miren Zulaica, Uxoa Fernandez-Pelayo, Mikel Munoz-Oreja, Miguel Urtasun, Ander Olaskoaga, Victoria Zelaya, Ivonne Jerico, Raquel Saez-Villaverde, Irene Catalina, Emma Sola, Elena Martinez-Saez, Aurora Pujol, Montserrat Ruiz, Agatha Schluter, Antonella Spinazzola, Jose Luis Munoz-Blanco, Francisco Grandas, Ian Holt, Victoria Alvarez, Adolfo Lopez de Munain
MOVEMENT DISORDERS
(2019)
Review
Endocrinology & Metabolism
Michio Hirano, Valerio Carelli, Roberto De Giorgio, Loris Pironi, Anna Accarino, Giovanna Cenacchi, Roberto D'Alessandro, Massimiliano Filosto, Ramon Marti, Francesco Nonino, Antonio Daniele Pinna, Elisa Baldin, Bridget Elizabeth Bax, Alessio Bolletta, Riccardo Bolletta, Elisa Boschetti, Matteo Cescon, Roberto D'Angelo, Maria Teresa Dotti, Carla Giordano, Laura Ludovica Gramegna, Michelle Levene, Raffaele Lodi, Hanna Mandel, Maria Cristina Morelli, Olimpia Musumeci, Alessia Pugliese, Mauro Scarpelli, Antonio Siniscalchi, Antonella Spinazzola, Galit Tal, Javier Torres-Torronteras, Luca Vignatelli, Irina Zaidman, Heinz Zoller, Rita Rinaldi, Massimo Zeviani
Summary: MNGIE is a rare autosomal recessive disease caused by TYMP mutations, leading to gastrointestinal and neurological symptoms. Diagnosis is challenging and treatment options are limited, with a need for standardized monitoring methods.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Alejandro Horga, Andreea Manole, Alice L. Mitchell, Enrico Bugiardini, Iain P. Hargreaves, Walied Mowafi, Conceicao Bettencourt, Emma L. Blakely, Langping He, James M. Polke, Catherine E. Woodward, Ilaria Dalla Rosa, Sachit Shah, Alan M. Pittman, Ros Quinlivan, Mary M. Reilly, Robert W. Taylor, Ian J. Holt, Michael G. Hanna, Robert D. S. Pitceathly, Antonella Spinazzola, Henry Houlden
Summary: Mutations in the MRPL44 gene can cause OXPHOS disorders and early-onset hypertrophic cardiomyopathy. A study found that a specific mutation in MRPL44 affects mitochondrial protein synthesis, leading to reduced levels of OXPHOS components and a multisystem disorder with neurological involvement. This study also identified complete maternal uniparental isodisomy of chromosome 2 in a patient with MRPL44-related disease.
MOLECULAR BIOLOGY REPORTS
(2021)
Article
Multidisciplinary Sciences
Boris Pantic, Daniel Ives, Mara Mennuni, Diego Perez-Rodriguez, Uxoa Fernandez-Pelayo, Amaia Lopez de Arbina, Mikel Munoz-Oreja, Marina Villar-Fernandez, Thanh-mai Julie Dang, Lodovica Vergani, Iain G. Johnston, Robert D. S. Pitceathly, Robert McFarland, Michael G. Hanna, Robert W. Taylor, Ian J. Holt, Antonella Spinazzola
Summary: By restricting the availability of glucose and glutamine, the authors have demonstrated that functional mitochondrial DNAs can be propagated while pathological variants are suppressed. The study shows that 2-Deoxy-D-glucose inhibits the replication of mutant mtDNA and glutamine withdrawal suppresses mtDNA synthesis in mutant cells. This highlights the importance of mitochondrial fitness in driving metabolite preference for mtDNA replication, offering potential interventions to suppress pathological mtDNAs.
NATURE COMMUNICATIONS
(2021)
Meeting Abstract
Clinical Neurology
D. Campo-Caballero, A. Spinazzola, E. Bugiardini, S. Efthymiou, H. Houlden, I. J. Holt, J. Rodriguez-Antiguedad, J. Equiza, P. Iruzubieta, J. F. Marti Masso, J. Ondaro, M. Zulaica, A. Lopez de Munain
EUROPEAN JOURNAL OF NEUROLOGY
(2020)
Article
Genetics & Heredity
Enrico Bugiardini, Olivia V. Poole, Andreea Manole, Alan M. Pittman, Alejandro Horga, Iain Hargreaves, Cathy E. Woodward, Mary G. Sweeney, Janice L. Holton, Jan-Willem Taanman, Gordon T. Plant, Joanna Poulton, Massimo Zeviani, Daniele Ghezzi, John Taylor, Conrad Smith, Carl Fratter, Meena A. Kanikannan, Arumugam Paramasivam, Kumarasamy Thangaraj, Antonella Spinazzola, Ian J. Holt, Henry Houlden, Michael G. Hanna, Robert D. S. Pitceathly
NEUROLOGY-GENETICS
(2017)