Article
Genetics & Heredity
Ty A. Bottorff, Heungwon Park, Adam P. Geballe, Arvind Rasi Subramaniam
Summary: Upstream open reading frames (uORFs) are present in over half of all human mRNAs and can regulate the translation of downstream open reading frames through various mechanisms. A study found that ribosome stalling in the first encountered uORF can prevent decreases in protein expression when ribosome loading onto mRNA is reduced. This buffering mechanism is insensitive to the location of the ribosome stall, and computational modeling suggests that colliding ribosomes dissociate rather than queue on the mRNA molecule.
Article
Biochemistry & Molecular Biology
Pedro do Couto Bordignon, Sebastian Pechmann
Summary: The translation of mRNAs into proteins by the ribosome is a crucial step in protein biosynthesis, tightly controlled to maintain cellular homeostasis. Ribosome profiling has provided insights into translation mechanisms, yet many aspects remain mysterious due to challenges in data interpretation. The study reveals programmed translational heterogeneity in genomic sequences, impacting cellular homeostasis and highlighting the complexity of translation regulation.
Article
Biochemistry & Molecular Biology
Martin B. D. Muller, Prasad Kasturi, Gopal G. Jayaraj, F. Ulrich Hartl
Summary: Research has found that reading through the 3' untranslated region (3' UTR) of DNA can lead to the production of abnormal proteins. However, the mechanisms by which eukaryotes effectively clear these abnormal proteins are still unclear. Through studying worms and mammalian cells, it was discovered that abnormal proteins are targeted by the BAG6 chaperone complex and the ribosome-collision-sensing protein GCN1 in a two-level quality control pathway. These findings define GCN1 as a key factor in maintaining protein homeostasis during translation.
Review
Biochemistry & Molecular Biology
Tom Joshua Eisenack, Debora Broch Trentini
Summary: Proteins are versatile molecular machines that control and execute cellular processes. They go through a multilayered synthesis process with many opportunities for error, and must navigate a complex folding-energy landscape. Newly synthesized proteins are at increased risk of misfolding and toxic aggregation, but cells employ molecular chaperones and quality control factors to maintain proteostasis.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Multidisciplinary Sciences
Daisuke Shimura, Jennifer Hunter, Makoto Katsumata, Robin M. Shaw
Summary: The CRISPR-Cas9 gene-editing system allows for the generation of gene-modified mouse models more efficiently than traditional methods, particularly for single-point mutations. In this study, a mutant mouse with a Gja1 point-mutation was generated to investigate the effect of residue 213 on Cx43 function.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2022)
Article
Neurosciences
Sherif Rashad, Shane R. Byrne, Daisuke Saigusa, Jingdong Xiang, Yuan Zhou, Liyin Zhang, Thomas J. Begley, Teiji Tominaga, Kuniyasu Niizuma
Summary: This study investigated the impact of blocking transcription or translation on Erastin (Class I) or RSL3 (Class II) induced ferroptosis. It was found that blocking transcription or translation protected cells against Erastin but was detrimental against RSL3. The study also revealed divergent mRNA stability changes and codon usage biases in cellular response to Erastin or RSL3. Additionally, the role of a tRNA modifying enzyme in the ferroptosis stress response was evaluated.
Article
Biochemistry & Molecular Biology
Richard She, Jingchuan Luo, Jonathan S. Weissman
Summary: We conducted genome-wide CRISPRi screens in human K562 cells to identify modulators of translation initiation frequency at near-cognate start codons. Depletion of any eIF3 core subunit promoted near-cognate start codon usage, with different sensitivity thresholds to sgRNA-mediated depletion. eIF3D depletion enhanced near-cognate usage through canonical eIF4E cap-binding, and not through eIF2A or eIF2D-dependent tRNA initiation. Disruption of eIF3D's cap-binding properties had no effect on start codon selection accuracy. Depletion of eIF3D also activated TNF alpha signaling via NF-kappa B and the interferon gamma response, similar to knockdown of eIF1A and eIF4G2. Our study provides new insights into alternative start codon usage mechanisms and consequences.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Leelavathi Sadhu, Krishan Kumar, Saravanan Kumar, Abhishek Dass, Ranjana Pathak, Amit Bhardwaj, Pankaj Pandey, Nguyen Van Cuu, Bhupendra S. Rawat, Vanga Siva Reddy
Summary: Chloroplasts have their own transcription and translation systems, similar to prokaryotic organisms. They use non-AUG start codons in protein synthesis, which is evolutionarily conserved from algae to angiosperms. The significance of non-AUG codons is not fully understood, and this study aims to unravel their importance using chloroplast genetic engineering.
SCIENTIFIC REPORTS
(2023)
Article
Genetics & Heredity
Erich Schaflinger, Jasmin Blatterer, Aiman Saeed Khan, Lukas Kaufmann, Lisa Auinger, Benjamin Tatrai, Sumra Wajid Abbasi, Muhammad Zeeshan Ali, Ansar Ahmad Abbasi, Ali Al Kaissi, Erwin Petek, Klaus Wagner, Muzammil Ahmad Khan, Christian Windpassinger
Summary: This study identified a novel mutation associated with MADB, which may rescue the function of the mutant protein by creating a new translation initiation site, explaining the relatively mild clinical outcome in the studied individuals.
Article
Genetics & Heredity
Erich Schaflinger, Jasmin Blatterer, Aiman Saeed Khan, Lukas Kaufmann, Lisa Auinger, Benjamin Tatrai, Sumra Wajid Abbasi, Muhammad Zeeshan Ali, Ansar Ahmad Abbasi, Ali Al Kaissi, Erwin Petek, Klaus Wagner, Muzammil Ahmad Khan, Christian Windpassinger
Summary: A novel N-terminal homozygous frameshift mutation (c.28_29insA) in ZMPSTE24 gene was identified in a consanguineous family segregating with MADB, possibly serving as a rescue mechanism in translation initiation.
Review
Biochemistry & Molecular Biology
Aishwarya Rana, Nidhi Gupta, Anil Thakur
Summary: Fungal pathogens utilize post-transcriptional and translational regulations to alter their protein pool, respond to stress, and undergo morphogenesis, ultimately influencing their virulence and survival. These regulatory mechanisms, mediated through mRNA elements and RNA-binding proteins, are potential targets for new therapeutics and are increasingly important in basic biology and drug discovery.
MOLECULAR ASPECTS OF MEDICINE
(2021)
Article
Biotechnology & Applied Microbiology
George Allen, Benjamin Weiss, Olesya O. O. Panasenko, Susanne Huch, Zoltan Villanyi, Benjamin Albert, Daniel Dilg, Marina Zagatti, Paul Schaughency, Susan E. E. Liao, Jeff Corden, Christine Polte, David Shore, Zoya Ignatova, Vicent Pelechano, Martine A. A. Collart
Summary: This study reveals the role of the Ccr4-Not complex in translation and the regulation of co-translational events by Not1 and Not4 through mRNA solubility.
Article
Plant Sciences
Jiao-Jiao Shi, Yuan Cao, Qiu-Hua Lang, Yao Dong, Liu-Yuan Huang, Liu-Jie Yang, Jing-Jing Li, Xue-Xin Zhang, Dan-Yang Wang
Summary: The nucleotide sequence context upstream of the AUG start codon has a significant impact on translation initiation efficiency in sperm cells, similar to somatic cells. However, unlike mammalian cells, there is no specific nucleotide site to regulate translation initiation efficiency in sperm cells.
PLANT REPRODUCTION
(2022)
Article
Biochemistry & Molecular Biology
Guillermo Lamolle, Andres Iriarte, Hector Musto
Summary: This study reanalyzed the codon usage in Schistosoma mansoni and discovered a significant increase of G/C-ending codons in highly expressed genes. Moreover, the synonymous distance was significantly lower in highly expressed genes compared to lowly expressed sequences. Therefore, the codon usage in S. mansoni is influenced by both mutational bias and translational selection.
MOLECULAR AND BIOCHEMICAL PARASITOLOGY
(2022)
Article
Biochemical Research Methods
Juri Sakata, Toshifumi Tatsumi, Akira Sugiyama, Akihiro Shimizu, Yuya Inagaki, Hiroto Katoh, Takefumi Yamashita, Kazuki Takahashi, Sho Aki, Yudai Kaneko, Takeshi Kawamura, Mai Miura, Masazumi Ishii, Tsuyoshi Osawa, Toshiya Tanaka, Shumpei Ishikawa, Masanobu Tsukagoshi, Michael Chansler, Tatsuhiko Kodama, Motomu Kanai, Hidetoshi Tokuyama, Kenzo Yamatsugu
Summary: This study reports an expression, refolding, and purification method for antibody-mimetic drug conjugate (AMDC). The AMDC uses a variable heavy chain of heavy chain-only antibodies (VHHs) as the targeting protein and non-covalently binds to a potent DNA-alkylating drug. The AMDC shows strong cytotoxic effects on cancer cells.
PROTEIN EXPRESSION AND PURIFICATION
(2024)
Article
Biochemical Research Methods
Yao Wang, Shaoting Weng, Yajie Tang, Sen Lin, Xiayue Liu, Wenhui Zhang, Gang Liu, Boomi Pandi, Yinrong Wu, Lei Ma, Lin Wang
Summary: In this study, a high yield of recombinant CD20 and claudin 18.2 proteins was achieved using an in vitro coupled transcription-translation system. The results showed that rituximab has a high affinity with CD20 protein. This study provides a novel concept for promoting the expression of multi-pass transmembrane proteins and lays the foundation for large-scale industrial production of membrane-associated drug targets.
PROTEIN EXPRESSION AND PURIFICATION
(2024)
Article
Biochemical Research Methods
Xiaobing Chen, Zijuan Zou, Wei Li, Xu Dong, Yi Chen, Yan Lu, Mingyue Zhu, Mengsen Li, Bo Lin
Summary: In this study, the fusion protein ImI-AFP3, composed of alpha-Conotoxin ImI and human alpha fetoprotein domain 3 (AFP3), was found to inhibit the growth and migration of lung cancer cells and showed synergistic effects with the drug gefitinib. These findings suggest that ImI-AFP3 is a promising candidate for the development of anticancer drugs.
PROTEIN EXPRESSION AND PURIFICATION
(2024)
Article
Biochemical Research Methods
Angel Castillo-Corujo, Mirva J. Saaranen, Lloyd W. Ruddock
Summary: This study successfully expressed two Fabs antibodies in the cytoplasm of E. coli using the CyDisCo system, achieving high yields and biological activity under industrially relevant fermentation conditions.
PROTEIN EXPRESSION AND PURIFICATION
(2024)
Article
Biochemical Research Methods
Junling Guo, Zhongyi Cheng, Zhemin Zhou
Summary: This study focused on a halophilic archaeal nitrile hydratase (NHase) and found that it exhibited higher tolerance to substrates and products compared to NHases from other sources. The unique genetic structure of this highly stable archaeal NHase could provide a theoretical foundation for modifying and enhancing the industrial application of NHase.
PROTEIN EXPRESSION AND PURIFICATION
(2024)
Article
Biochemical Research Methods
Yunlong Shen, Ruirui Zhang, Xiaohua Jiang, Jinliang Yang
Summary: The study developed a monoclonal antibody, B1M023, that can bind to LILRB1 with high affinity and block its binding to HLA-G. This antibody can promote the activation and IFN-gamma secretion of T cells, suggesting its potential applications in concomitant diagnosis and tumor immunotherapy.
PROTEIN EXPRESSION AND PURIFICATION
(2024)
Article
Biochemical Research Methods
Jun Jiang, Zhengqiang Jiang, Qiaojuan Yan, Susu Han, Shaoqing Yang
Summary: A novel alginate lyase gene from a marine bacterium showed efficient enzyme activity and stability, producing high conversion ratios of alginate oligosaccharides.
PROTEIN EXPRESSION AND PURIFICATION
(2024)
Article
Biochemical Research Methods
Xianghua Xiong, Yujin Qiu, Jiahao Zheng, Ling Zhou, Qingyang Wang, Jinglun Pang, Weicai Zhang, Huipeng Chen, Gang Liu, Xiaodong Han
Summary: A specific monoclonal antibody ML419 has been found to disrupt the recognition between Botulinum neurotoxin serotype A (BoNT/A) and FGFR3, effectively preventing BoNT/A from entering neurons. In vivo experiments show that ML419 has a strong protective effect, making it a promising candidate for the development of therapeutics against BoNT/A.
PROTEIN EXPRESSION AND PURIFICATION
(2024)
Article
Biochemical Research Methods
Maria Rain Jennings, Soohyon Min, Grace S. Xu, Kassandra Homayuni, Bhavana Suresh, Yusef Amir Haikal, John Blazeck
Summary: This study successfully produced Homo sapiens adenosine deaminase isoform 1 (HsADA1) and its variants through optimizing the recombinant expression process. The D8N variant of HsADA1 was found to be about 30% less active than the wildtype, but it better retained its activity in human serum. Additionally, the study revealed a previously undescribed phenomenon involving albumin that contributed to the increased activity of HsADA1 and the D8N variant in serum.
PROTEIN EXPRESSION AND PURIFICATION
(2024)
Article
Biochemical Research Methods
Oinam Sangita Devi, Senjam Sunil Singh, K. Rana, Sorokhaibam Jibankumar Singh, Wayenbam Sobhachandra Singh
Summary: A new lectin with hemagglutination activity was purified from the rhizome of Xanthosoma violaceum Schott. The lectin showed different reactions towards human red blood cells of different blood groups. It exhibited optimal hemagglutination activity at specific temperature and pH range, and showed good stability.
PROTEIN EXPRESSION AND PURIFICATION
(2024)