Article
Biochemistry & Molecular Biology
Yuhei Chadani, Nobuyuki Sugata, Tatsuya Niwa, Yosuke Ito, Shintaro Iwasaki, Hideki Taguchi
Summary: Translation elongation is essential for organisms to produce their proteomes, but there is a risk of elongation abortion due to sequences like intrinsic ribosome destabilization (IRD) sequences. Most potential IRD sequences in the middle of open reading frames remain hidden and do not interrupt translation, as the nascent polypeptide itself acts as a bridge in the ribosome, protecting it from dissociation. This inherent ability of nascent polypeptide products ensures elongation continuity.
Article
Neurosciences
Mina N. Anadolu, Jingyu Sun, Senthilkumar Kailasam, Kleanthi Chalkiadaki, Konstanze Krimbacher, Jewel T. -Y. Li, Teodora Markova, Seyed M. Jafarnejad, Francois Lefebvre, Joaquin Ortega, Christos G. Gkogkas, Wayne S. Sossin
Summary: The granule fraction contains proteins implicated in stalled polysome function, and the ribosomes in this fraction are mainly stalled in the hybrid state. Ribosome profiling reveals longer footprints on mRNAs associated with FMRPs and an increase in ribosome occupancy on mRNAs encoding RNA binding proteins. The data supports a model in which specific sequences in mRNAs stall ribosomes during translation elongation in neurons.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Microbiology
Nikhil Bose, Sean D. Moore
Summary: This study challenges the belief that 16S rRNA gene variable region sequences provide little information for intra-genus classification and that single nucleotide variations within them are inconsequential. The researchers found that even small sequence changes in variable regions can negatively affect the performance of 16S rRNA in Escherichia coli. Additionally, they discovered that certain Escherichia and Shigella species can be distinguished using a multi-allelic 16S rRNA variable region single nucleotide polymorphism (SNP). The study emphasizes the importance of considering variable region sequences in taxonomic assignments and highlights the potential for multiple 16S rRNA gene alleles to provide more detailed phylogenetic and taxonomic information.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biochemistry & Molecular Biology
Nobuyuki Shimohata, Yudai Harada, Toshiya Hayano
Summary: This study comprehensively examined translationally arrested nascent polypeptides in mammalian cells, providing novel insights into the mechanism of ribosomal arrest peptides (RAPs) in mammalian cells.
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Surajit Chatterjee, Adrien Chauvier, Shiba S. Dandpat, Irina Artsimovitch, Nils G. Walter
Summary: In bacteria, the interaction between RNA polymerase and ribosome regulates gene expression through transcription-translation coupling. This coupling is mainly achieved by RNA polymerase promoting the binding of the ribosomal 30S subunit to antagonize ribosome binding site occlusion induced by a riboswitch, thereby facilitating translation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
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)
Article
Multidisciplinary Sciences
Ruiyue Tan, Margaret Hoare, Kevin A. Welle, Kyle Swovick, Jennifer R. Hryhorenko, Sina Ghaemmaghami
Summary: The folding of proteins during translation while bound to the ribosome is not well understood. This study developed a method using mass spectrometry to measure the stability of nascent polypeptide chains. The results showed that the ribosome significantly influences the stability of the nascent polypeptides, with variations depending on different folding domains and localized charge distributions within the polypeptides. The study suggests that electrostatic interactions between the ribosome and nascent polypeptides play a role in these stability modulations.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Maximilian Seidel, Natalie Romanov, Agnieszka Obarska-Kosinska, Anja Becker, Nayara Trevisan Doimo de Azevedo, Jan Provaznik, Sankarshana R. Nagaraja, Jonathan J. M. Landry, Vladimir Benes, Martin Beck
Summary: Various cellular quality control mechanisms are involved in maintaining protein homeostasis. In addition to preventing misfolding during translation, ribosome-associated chaperones and importins also play roles in preventing protein aggregation and facilitating nucleocytoplasmic transport. This study suggests that importins can bind to ribosome-associated cargoes in a co-translational manner, including proteins such as ribosomal proteins, chromatin remodelers, and RNA binding proteins that are prone to cytosolic aggregation. The authors also demonstrate that importins act consecutively with other ribosome-associated chaperones, highlighting the interconnectedness of the nuclear import system and nascent chain folding.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Chien- Yang, Jiwoo Kim, Shu-Ou Shan
Summary: The ribosome actively participates in diverse protein biogenesis pathways, including folding, localization, and modifications. It imposes an additional layer of substrate selection during N-terminal methionine excision (NME) in bacteria.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Jan Philip Wurm, Katarzyna-Anna Glowacz, Remco Sprangers
Summary: DbpA, an ATP-dependent DEAD-box RNA helicase from Escherichia coli, plays a crucial role in ribosome biogenesis. By binding to hairpin 92 of the 23S rRNA, DbpA's activity is endorsed, indicating its importance in the maturation of ribosomes. The study elucidates how DbpA interacts with maturing ribosomes and the regulatory mechanism that modulates its activity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Genetics & Heredity
Samantha Lin, Suchita Rajan, Sofia Lemberg, Mark Altawil, Katherine Anderson, Ruth Bryant, Sebastian Cappeta, Brandon Chin, Isabella Hamdan, Annelise Hamer, Rachel Hyzny, Andrew Karp, Daniel Lee, Alexandria Lim, Medha Nayak, Vishnu Palaniappan, Soomin Park, Sarika Satishkumar, Anika Seth, Uva Sri Dasari, Emili Toppari, Ayush Vyas, Julianne Walker, Evan Weston, Atif Zafar, Cecelia Zielke, Ganapati H. Mahabeleshwar, Alan M. Tartakoff
Summary: 35S rRNA transcripts are precursors to the small and large ribosomal subunits and undergo processing to yield massive precursors that include assembly factor proteins. Nucleolar assembly factors form layers around ribosomal DNA, and most of them are cyclically recruited between latent and operative states. These factors are highly conserved and show similarities to subcompartments found in higher eukaryotic cells. Our proposed 3-step subdomain assembly model suggests that basic assembly factors sequentially nucleate sites along nascent rRNA, followed by recruiting less basic assembly factors and ribosomal proteins, and finally consolidating the rRNPs in nearby subdomains.
Article
Biochemistry & Molecular Biology
Junki Uchiyama, Yasushi Ishihama, Koshi Imami
Summary: The development of a clickable puromycin analogue, OPP, allows for labeling nascent polypeptide chains and proteomic analysis of NPCs, enabling accurate quantitative profiling of nascent proteins.
JOURNAL OF BIOCHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Markus Hopfler, Ramanujan S. Hegde
Summary: Cells regulate mRNA processing, localization, and stability to ensure accurate gene expression. Recent discoveries have uncovered co-translational mechanisms that modulate mRNA translation, localization, processing, and stability. These mechanisms operate by recognizing the nascent protein and directing mRNA fate, allowing cells to dynamically regulate their transcriptomes in response to cellular changes.
Article
Multidisciplinary Sciences
Phillip C. Burke, Heungwon Park, Arvind Rasi Subramaniam
Summary: By measuring the effects of thousands of coding sequence motifs on mRNA levels in human cells, the authors identify nascent peptides with a combination of extended beta-strand structures and bulky, positively charged sequences that reduce mRNA levels by slowing translation.
NATURE COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Kazuya Ichihara, Keiichi Nakayama, Akinobu Matsumoto
Summary: Recent studies have shown that some RNAs annotated as noncoding RNAs can actually be translated into shorter polypeptides, and many proteins are translated from non-traditional initiation codons. The identification of unannotated protein-coding sequences involves techniques such as ribosome profiling and mass spectrometry, and these sequences play important roles in physiological processes.
JOURNAL OF BIOCHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Sara K. Young, Lakshmi Reddy Palam, Cheng Wu, Matthew S. Sachs, Ronald C. Wek
JOURNAL OF BIOLOGICAL CHEMISTRY
(2016)
Article
Multidisciplinary Sciences
Stephen Z. Caster, Kathrina Castillo, Matthew S. Sachs, Deborah Bell-Pedersen
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2016)
Article
Genetics & Heredity
Rigzin Dekhang, Cheng Wu, Kristina M. Smith, Teresa M. Lamb, Matthew Peterson, Erin L. Bredeweg, Oneida Ibarra, Jillian M. Emerson, Nirmala Karunarathna, Anna Lyubetskaya, Elham Azizi, Jennifer M. Hurley, Jay C. Dunlap, James E. Galagan, Michael Freitag, Matthew S. Sachs, Deborah Bell-Pedersen
G3-GENES GENOMES GENETICS
(2017)
Article
Microbiology
Ivaylo P. Ivanov, Jiajie Wei, Stephen Z. Caster, Kristina M. Smith, Audrey M. Michel, Ying Zhang, Andrew E. Firth, Michael Freitag, Jay C. Dunlap, Deborah Bell-Pedersen, John F. Atkins, Matthew S. Sachs
Article
Biochemical Research Methods
Cheng Wu, Ananya Dasgupta, Lunda Shen, Deborah Bell-Pedersen, Matthew S. Sachs
Article
Biochemistry & Molecular Biology
Qian Yang, Chien-Hung Yu, Fangzhou Zhao, Yunkun Dang, Cheng Wu, Pancheng Xie, Matthew S. Sachs, Yi Liu
NUCLEIC ACIDS RESEARCH
(2019)
Article
Biochemistry & Molecular Biology
Jerusha Salome Emmanuel, Arnab Sengupta, Emily Roth Gordon, Joseph Thomas Noble, Luis Rogelio Cruz-Vera
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Article
Multidisciplinary Sciences
Anne-Xander van der Stel, Emily R. Gordon, Arnab Sengupta, Allyson K. Martinez, Dorota Klepacki, Thomas N. Perry, Alba Herrero del Valle, Nora Vazquez-Laslop, Matthew S. Sachs, Luis R. Cruz-Vera, C. Axel Innis
Summary: The study identifies a mechanism where the TnaC-ribosome complex captures L-Trp to initiate termination arrest, with nascent TnaC preventing release factor 2 from adopting an active conformation. The relative rates of L-Trp binding and peptidyl-tRNA cleavage determine the tryptophan sensitivity of each variant. This reveals a strategy whereby a nascent peptide assists the ribosome in detecting a small metabolite.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Lunda Shen, Zhaoming Su, Kailu Yang, Cheng Wu, Thomas Becker, Deborah Bell-Pedersen, Junjie Zhang, Matthew S. Sachs
Summary: The study elucidated the mechanism of action of CHX in inhibiting protein synthesis by arresting the ribosome in the classical PRE translocation state, without interfering with A-site reactivity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Microbiology
Sarah B. Worthan, Elizabeth A. Franklin, Chi Pham, Mee-Ngan F. Yap, Luis R. Cruz-Vera
Summary: Mutations in bacterial ribosomes can affect gene expression and bacterial fitness. This study focuses on the effects of uL22(K90D) mutant ribosomal protein on gene expression and phenotype in Escherichia coli. The mutant ribosomes resulted in reduced expression of genes involved in catabolism, acid resistance, and biofilm formation. These changes led to increased survival in acidic conditions and enhanced biofilm formation.
MICROBIOLOGY SPECTRUM
(2022)
Article
Microbiology
Matthew R. Breuer, Ananya Dasgupta, Joseph G. Vasselli, Xiaorong Lin, Brian D. Shaw, Matthew S. Sachs
Summary: The prevalence and increasing incidence of fungal infections globally is a significant worldwide health problem. Cryptococcosis, primarily caused by the pathogenic yeast Cryptococcus neoformans, is responsible for approximatelyestimated deaths annually. The scarcity of treatments and the increasing resistance to current therapeutics highlight the need for the development of antifungal agents which have novel mechanisms of action and are suitable for clinical use. Repurposing existing FDA-approved compounds as antimycotic therapeutics is a promising strategy for the rapid development of such new treatments. Sertraline (SRT), a commonly prescribed antidepressant, is a broad-spectrum antifungal agent with particular efficacy against C. neoformans. However, the effect of SRT on fungal physiology is not understood. Here, we report that SRT induces the formation of supersized lipid droplets (SLDs) in C. neoformans, and in Candida albicans, Saccharomyces cerevisiae, and Aspergillus fumigatus. SLDs were not induced in C. neoformans by treatment with the antifungal fluconazole (FLC), consistent with SRT and FLC acting differently to perturb C. neoformans physiology. The formation of SLDs in response to SRT indicates that this compound alters the lipid metabolism of C. neoformans. Moreover, the SRT-induced enlargement of LDs in other fungal species may indicate a common fungal response to SRT.
Article
Microbiology
Flaviane M. Galvao-Rocha, Carlos H. L. Rocha, Maira P. Martins, Pablo R. Sanches, Tamires A. Bitencourt, Matthew S. Sachs, Nilce M. Martinez-Rossi, Antonio Rossi
Summary: SRT alters gene expression related to fungal cell wall and plasma membrane stability, energy metabolism, detoxification, and defense against oxidative stress in T. rubrum, providing potential targets for its use in treating dermatophytosis.
Article
Biotechnology & Applied Microbiology
Maria Stavrianakou, Ricardo Perez, Cheng Wu, Matthew S. Sachs, Rodolfo Aramayo, Mark Harlow
Article
Genetics & Heredity
Huinan Li, Cheng Wu, Rodolfo Aramayo, Matthew S. Sachs, Mark L. Harlow