Article
Multidisciplinary Sciences
Amila Zuko, Moushami Mallik, Robin Thompson, Emily L. Spaulding, Anne R. Wienand, Marije Been, Abigail L. D. Tadenev, Nick van Bakel, Celine Sijlmans, Leonardo A. Santos, Julia Bussmann, Marica Catinozzi, Sarada Das, Divita Kulshrestha, Robert W. Burgess, Zoya Ignatova, Erik Storkebaum
Summary: Heterozygous mutations in six transfer RNA synthetase genes cause Charcot-Marie-Tooth peripheral neuropathy. Mutant tRNA synthetases in CMT inhibit protein synthesis by binding tRNA(Gly) but failing to release it, leading to tRNAGly sequestration and ribosome stalling. Overexpression of tRNA(Gly) rescues protein synthesis, peripheral neuropathy, and ISR activation, suggesting therapeutic potential in CMT2D.
Article
Multidisciplinary Sciences
Jiaqiang Zhu, Wei Huang, Jing Zhao, Loc Huynh, Derek J. Taylor, Michael E. Harris
Summary: This study reveals the conformational changes during the recognition process of bacterial RNase P using high-throughput enzymology and cryoEM. The specific pairing of precursor tRNA inhibits the formation of the catalytic conformation. Comparisons of different precursor tRNA structures show that RNase P primarily uses stacking interactions and shape complementarity to accommodate alternative sequences. The study uncovers the active site interactions and conformational changes of RNase P, laying the foundation for understanding the link between binding interactions and catalysis.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Jennifer Porat, Ana Vakiloroayaei, Brittney M. Remnant, Mohammadaref Talebi, Taylor Cargill, Mark A. Bayfield
Summary: tRNAs undergo posttranscriptional modifications that are important for their stability and native fold. Impaired posttranscriptional modification can lead to human diseases by affecting translation, mitochondrial function, and tRNA degradation. Recent evidence suggests that bacterial tRNA modification enzymes can act as chaperones to guide tRNA folding independently of their catalytic activity. In this study, the tRNA methyltransferase Trm1 is shown to promote tRNA functionality even without catalytic activity. These findings expand our understanding of the role of tRNA modification enzymes and how the RNA chaperone La influences tRNA modification.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Cell Biology
Yanyan Cao, Kai Liu, Ying Xiong, Chunyue Zhao, Lei Liu
Summary: Excessive release of glutamate can cause neuronal necrosis in ischemic stroke. This study found that an increase in H3K4 trimethylation leads to the accumulation of tRNA-derived fragments and piRNAs in glutamate-induced neuronal necrosis, ultimately resulting in cell death. The toxic effect of tRFs may be due to the inhibition of protein synthesis through ribosomal stalling and disruption of mitochondrial metabolism, while abnormal transcription of tRFs may play a crucial role in neuronal necrosis.
CELL DEATH & DISEASE
(2021)
Article
Cell Biology
Rebecca Brogli, Marina Cristodero, Andre Schneider, Norbert Polacek
Summary: The tRNAThr-3'-half is a non-coding RNA that enhances translation and is generated inside the mitochondria during starvation. It associates with mitochondrial ribosomes and stimulates translation during stress recovery, promoting mitochondrial activity and cellular energy production.
Article
Engineering, Environmental
Zhihang Yuan, Zhongyue Zhou, Haiping Yuan, Nanwen Zhu, Ziyang Lou
Summary: The composition of sewage sludge and the correlation between its components and pyrolysis products were investigated in this study. Protein, polysaccharide, and humic acid were found to be the major organic components in sludge, with different contributions to the pyrolysis products. The main contributor to carbonaceous components in char shifted from protein to humic acid as the temperature increased. Tar and gas products were mainly originated from protein and polysaccharide at temperatures above 550 degrees C. The presence of calcium/silicon/aluminum-containing inorganics and polyferric chloride influenced the formation of nitrogenous tars and NOx.
CHEMICAL ENGINEERING JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Karolina Michalska, Robert Jedrzejczak, Jacek Wower, Changsoo Chang, Beatriz Baragana, Ian H. Gilbert, Barbara Forte, Andrzej Joachimiak
Summary: Tuberculosis, caused by Mycobacterium tuberculosis, is the deadliest infectious disease responsible for around 1.5 million deaths in 2018. The global spread of multidrug resistant strains poses a public health threat that requires new treatments. Aminoacyl-tRNA synthetases are potential drug targets due to their essential role in protein synthesis, providing insights for the development of anti-tuberculosis drugs.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Jitendra Singh, Rishi Kumar Mishra, Shreya Ahana Ayyub, Tanweer Hussain, Umesh Varshney
Summary: This study reveals the crucial role of the interaction between the N-terminal domain (NTD) of initiation factor 3 (IF3) and initiator tRNA (i-tRNA) in bacterial translation initiation and growth fitness of Escherichia coli. Specific mutations in NTD disrupt its interaction with i-tRNA, leading to impaired translation fidelity and bacterial growth.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Yangyang Li, Shichen Su, Yanqing Gao, Guoliang Lu, Hehua Liu, Xi Chen, Zhiwei Shao, Yixi Zhang, Qiyuan Shao, Xin Zhao, Jie Yang, Chulei Cao, Jinzhong Lin, Jinbiao Ma, Jianhua Gan
Summary: In this study, the crystal structure of HARP proteins and their mechanism of pre-tRNA binding and cleavage were elucidated. The results showed that HARP proteins can undergo conformational changes to facilitate pre-tRNA binding and catalytic site formation, and can assemble into larger oligomers. The study also revealed a cooperative pre-tRNA processing mode, where one HARP dimer binds pre-tRNA at the elbow region and 5'-end removal is catalyzed by the partner dimer.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Sameer Dixit, Alan C. Kessler, Jeremy Henderson, Xiaobei Pan, Ruoxia Zhao, Gabriel Silveira D'Almeida, Sneha Kulkarni, Mary Anne T. Rubio, Eva Hegedusova, Robert L. Ross, Patrick A. Limbach, Brian D. Green, Zdenek Paris, Juan D. Alfonzo
Summary: Research shows that the levels of tRNA Q in Trypanosoma brucei dynamically change in response to variations in amino acid concentrations, particularly tyrosine. These changes have negligible effects on global translation or growth rate, but can impact codon choice in tRNA(Tyr).
NUCLEIC ACIDS RESEARCH
(2021)
Editorial Material
Cell Biology
Saori Uematsu, Shu-Bing Qian
Summary: The bacterial pathogen Legionella pneumophila utilizes the effector SidI to enhance pathogenesis within host cells by employing dual mechanisms. The N-terminal domain of SidI mimics tRNA, while the C-terminal domain glycosylates the ribosome.
NATURE CELL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Natalie Krahn, Jingji Zhang, Sergey Melnikov, Jeffery M. Tharp, Alessandra Villa, Armaan Patel, Rebecca J. Howard, Haben Gabir, Trushar R. Patel, Jorg Stetefeld, Joseph Puglisi, Dieter Soll
Summary: Protein translation is achieved through tRNA aminoacylation and ribosomal elongation. This study explores the tRNA identity elements for a Delta pylSn tRNA(Pyl) and identifies five key elements necessary for MaPylRS activity.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Olga A. Esakova, Tyler L. Grove, Neela H. Yennawar, Arthur J. Arcinas, Bo Wang, Carsten Krebs, Steven C. Almo, Squire J. Booker
Summary: Numerous post-transcriptional modifications of transfer RNAs play critical roles in translation, with the ms(2)i(6)A modification by MiaB being essential for enhancing translational fidelity. This work provides insight into the mechanism by which MiaB functionalizes inert C-H bonds with sulfur, through a two-step process involving radical SAM chemistry and sulfur transfer mediated by an auxiliary cluster.
Article
Biochemistry & Molecular Biology
Koushick Sivakumar, Vinitha Lakshmi Venkadasamy, Gurumoorthy Amudhan, Kezia J. Ann, Gadela Karteek Goud, Kiranmai Nayani, Jotin Gogoi, Santosh Kumar Kuncha, Prathama S. Mainkar, Shobha P. Kruparani, Rajan Sankaranarayanan
Summary: The homochirality of cellular proteome is determined by the L-chiral bias of the translation apparatus. Enzyme chiral specificity was explained by the 'four-location' model proposed by Koshland. In this study, the authors show through in vitro and in vivo experiments coupled with structural analysis that alanyl-tRNA synthetase (AlaRS) strictly rejects D-alanine at its catalytic site, and that the editing domain of AlaRS is responsible for correcting L-serine and glycine mischarging, rather than the D-aminoacyl-tRNA deacylase.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Sabrina M. Huber, Ulrike Begley, Anwesha Sarkar, William Gasperi, Evan T. Davis, Vasudha Surampudi, May Lee, J. Andres Melendez, Peter C. Dedon, Thomas J. Begley
Summary: Cells respond to environmental stress by regulating gene expression at the level of both transcription and translation. The dynamic regulation of transfer RNA (tRNA) wobble modifications leads to selective translation of stress response proteins. This study reveals that the response of human hepatocellular carcinoma cells to arsenite exposure is regulated by the availability of queuine, a precursor to tRNA wobble modification. Limiting queuine leads to cell death, altered translation, increased reactive oxygen species levels, and mitochondrial dysfunction.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Nathan H. Blewett, James R. Iben, Sergei Gaidamakov, Richard J. Maraia
MOLECULAR AND CELLULAR BIOLOGY
(2017)
Article
Biochemistry & Molecular Biology
Jyotsna Vinayak, Stefano A. Marrella, Rawaa H. Hussain, Leonid Rozenfeld, Karine Solomon, Mark A. Bayfield
NUCLEIC ACIDS RESEARCH
(2018)
Article
Biochemistry & Molecular Biology
Saviz Ehyai, Tetsuaki Miyake, Declan Williams, Jyotsna Vinayak, Mark A. Bayfield, John C. McDermott
Article
Biochemistry & Molecular Biology
Stefano A. Marrella, Kerene A. Brown, Farnaz Mansouri-Noori, Jennifer Porat, Derek J. Wilson, Mark A. Bayfield
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Review
Biochemistry & Molecular Biology
Mark A. Bayfield, Jyotsna Vinayak, Kyra Kerkhofs, Farnaz Mansouri-Noori
Summary: La protein shuttles between the nucleus and cytoplasm to bind nascent RNA polymerase III transcripts and mRNAs using different binding modes, protecting RNA precursors and promoting maturation and translation. Studies have shown that La proteins utilize multiple binding modes beyond the well-characterized UUU-3' end recognition, expanding our understanding of their RNA chaperone activity.
Editorial Material
Biochemistry & Molecular Biology
Mark A. Bayfield, Kyra Kerkhofs, Farnaz Mansouri-Noori
Article
Multidisciplinary Sciences
Jonah Beenstock, Samara Mishelle Ona, Jennifer Porat, Stephen Orlicky, Leo C. K. Wan, Derek F. Ceccarelli, Pierre Maisonneuve, Rachel K. Szilard, Zhe Yin, Dheva Setiaputra, Daniel Y. L. Mao, Morgan Khan, Shaunak Raval, David C. Schriemer, Mark A. Bayfield, Daniel Durocher, Frank Sicheri
NATURE COMMUNICATIONS
(2020)
Editorial Material
Biochemistry & Molecular Biology
Sarah P. Blagden, Mark Bayfield, Cecile Bousquet-Antonelli
Review
Biochemistry & Molecular Biology
Jennifer Porat, Ute Kothe, Mark A. Bayfield
Summary: tRNAs undergo posttranscriptional modifications that influence their secondary and tertiary interactions, with key modifications being crucial for structural integrity. In addition to tRNA modifications, tRNA chaperones such as the La protein play a role in promoting correct tRNA folding and protecting it from degradation. Some tRNA modification enzymes also exhibit tRNA folding activity distinct from their catalytic function, suggesting a potential role as tRNA chaperones.
Article
Multidisciplinary Sciences
Jennifer Porat, Moaine El Baidouri, Jorg Grigull, Jean-Marc Deragon, Mark A. Bayfield
Summary: The methyl phosphate capping enzyme Bmc1/Bin3 is identified as a stable component of the S. pombe telomerase holoenzyme. It is involved in the assembly of the telomerase holoenzyme by promoting TER1 accumulation and Pof8 recruitment. This study provides new insights into the composition, assembly, and evolutionary conservation of the telomerase holoenzyme.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Kyra Kerkhofs, Jyoti Garg, Etienne Fafard-Couture, Sherif Abou Elela, Michelle S. Scott, Ronald E. Pearlman, Mark A. Bayfield
Summary: Studies have shown that the Tetrahymena thermophila protein Mlp1 plays a key role in La protein function, affecting pre-tRNA processing and stability of 3'-trailers when depleted. The short length of 3'-trailers in Tetrahymena thermophila compared to other eukaryotes, along with the evolution of 5'-leaders disfavoring pre-tRNA leader/trailer pairing, indicate a unique mechanism of tRNA processing in Tetrahymena thermophila associated with the variant architecture of Mlp1.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Jennifer Porat, Ana Vakiloroayaei, Brittney M. Remnant, Mohammadaref Talebi, Taylor Cargill, Mark A. Bayfield
Summary: tRNAs undergo posttranscriptional modifications that are important for their stability and native fold. Impaired posttranscriptional modification can lead to human diseases by affecting translation, mitochondrial function, and tRNA degradation. Recent evidence suggests that bacterial tRNA modification enzymes can act as chaperones to guide tRNA folding independently of their catalytic activity. In this study, the tRNA methyltransferase Trm1 is shown to promote tRNA functionality even without catalytic activity. These findings expand our understanding of the role of tRNA modification enzymes and how the RNA chaperone La influences tRNA modification.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Jennifer Porat, Viktor A. Slat, Stephen D. Rader, Mark A. Bayfield
Summary: Splicing requires tight coordination between dynamic spliceosomal RNAs and proteins. In this study, the authors found that Bmc1 and Pof8 play important roles in the formation of a distinct U6 snRNP that promotes U6 2'-O-methylation, and identified a non-canonical snoRNA guiding this methylation. They also discovered that the 5' γ-monomethyl phosphate capping activity of Bmc1 is not required for its role in promoting snoRNA-guided 2'-O-methylation. These findings provide insights into the novel functions of Bmc1/MePCE family members and the general role of Bmc1 and Pof8 in guiding noncoding RNP assembly.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Cell Biology
Farnaz Mansouri-Noori, Andreas Pircher, Danielle Bilodeau, Lidia Siniavskaia, Jorg Grigull, Olivia S. Rissland, Mark A. Bayfield
Summary: This study reveals that the fission yeast LARP1 homolog, Slr1p, controls the translation and stability of mRNAs encoding proteins similar to 5'TOP mRNAs in higher eukaryotes. It suggests that the LARP1 DM15 motif and the mRNA 5'TOP motif may be features that were formed based on a more fundamental mechanism of LARP1-associated control of gene expression.
Review
Biochemistry & Molecular Biology
Richard J. Maraia, Aneeshkumar G. Arimbasseri
