Article
Biochemistry & Molecular Biology
Youssef El Mouali, Milan Gerovac, Raminta Mineikaite, Joerg Vogel
Summary: FinO-domain proteins, as an emerging family of RNA-binding proteins, have diverse roles in bacterial post-transcriptional control and physiology, with the ability to act selectively or promiscuously on the same cellular RNA pool. The study extensively profiled cellular transcripts associated with the virulence plasmid-encoded FinO in Salmonella, identifying two major ligands: FinP and RepX. The research also observed cross-regulation of plasmids on the RNA level, with the FinO RBP controlling the replication of an antibiotic resistance plasmid in Salmonella.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Agnieszka Kiliszek, Wojciech Rypniewski, Leszek Blaszczyk
Summary: The p53 protein is an essential regulator for maintaining cellular homeostasis under stress conditions. This study investigates the structural determinants of long-range RNA-RNA interactions in p53 mRNA and the role of nucleolin in facilitating these interactions. The 8-nt bulge motif is identified as a key structural element in base-pairing of complementary sequences in p53 mRNA, and nucleolin is found to promote this base-pairing through its RNA chaperone activity. Mutational analysis reveals that all four RNA recognition motifs of nucleolin are indispensable for its optimal RNA chaperone activity. These findings provide insights into the unique mechanism of p53 protein translation regulation and the importance of the bulge motif and nucleolin in intramolecular RNA-RNA recognition in p53 mRNA.
Article
Food Science & Technology
Thais Caldas Paiva Moreira, Rosiane Lopes da Cunha
Summary: This study evaluated the effect of ultrasound on the control of whey proteins (WPI) aggregation and investigated the gelation properties of ultrasound-treated proteins. The results showed that higher power values and shorter times of ultrasound treatment could result in greater protein changes that affected gelation characteristics. This suggests that the modulation of ultrasound conditions can produce ingredients with different techno-functional properties.
FOOD RESEARCH INTERNATIONAL
(2023)
Article
Multidisciplinary Sciences
Siwy Ling Yang, Louis DeFalco, Danielle E. Anderson, Yu Zhang, Jong Ghut Ashley Aw, Su Ying Lim, Xin Ni Lim, Kiat Yee Tan, Tong Zhang, Tanu Chawla, Yan Su, Alexander Lezhava, Andres Merits, Lin-Fa Wang, Roland G. Huber, Yue Wan
Summary: The study identified functional structural elements within the SARS-CoV-2 genome, showed differences in RNA folding between wildtype and mutant viruses, and found hundreds of RNA-RNA interactions within the virus genome and between virus and host RNAs. The virus genome strongly binds to mitochondrial and small nucleolar RNAs and undergoes extensive 2'-O-methylation.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Alisa Rizvanovic, Jonas Kjellin, Fredrik Soderbom, Erik Holmqvist
Summary: The N-terminal domain of the global RNA-binding protein ProQ plays a crucial role in RNA binding activity, while the function of the C-terminal domain remains unclear, indicating an essential role of the C-terminal domain in gene regulation.Mutation of conserved CTD residues leads to overstabilization of RNA targets and renders ProQ inert in regulation, without affecting protein stability in vivo.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Alisa Rizvanovic, Jonas Kjellin, Fredrik Soderbom, Erik Holmqvist
Summary: The global RNA-binding protein ProQ plays a central role in post-transcriptional regulatory networks in bacteria, with its N-terminal domain being essential for RNA-binding activity. Through extensive mutagenesis studies, critical residues in both the NTD and CTD of ProQ have been identified, highlighting the importance of RNA-binding activity for regulatory capacity. Additionally, mutations in the NTD were found to lead to cellular instability of ProQ, suggesting that interaction with RNA protects the protein from degradation. Meanwhile, mutation of conserved CTD residues resulted in overstabilization of RNA targets and loss of regulatory function, indicating an essential role for the ProQ CTD in gene regulation.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Microbiology
Anna Maria Giuliodori, Riccardo Belardinelli, Melodie Duval, Raffaella Garofalo, Emma Schenckbecher, Vasili Hauryliuk, Eric Ennifar, Stefano Marzi
Summary: Escherichia coli CspA is an RNA binding protein that stimulates translation, including its own, during cold-shock. It specifically promotes the translation of cspA mRNA at low temperature by interacting with the folded conformation less accessible to the ribosome without inducing large structural rearrangements. This interaction allows the progression of ribosomes during the transition from translation initiation to elongation, and a similar mechanism may be responsible for CspA-dependent translation stimulation observed with other probed mRNAs.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Oncology
Kellie A. Cotter, John Gallon, Nadine Uebersax, Philip Rubin, Kate D. Meyer, Salvatore Piscuoglio, Samie R. Jaffrey, Mark A. Rubin
Summary: Recent evidence suggests that N-6-methyladenosine plays a significant role in cancer, particularly in prostate cancer where low levels of METTL3 are associated with advanced metastatic disease. METTL3 knockdown in prostate cancer cells leads to resistance to androgen receptor antagonists via a mechanism involving upregulation of nuclear receptor NR5A2/LRH-1.
MOLECULAR CANCER RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Shinsuke Yasuda, Risa Kobayashi, Toshiro Ito, Yuko Wada, Seiji Takayama
Summary: The trait of self-incompatibility (SI) is conserved among members of the Brassicaceae plant family, controlled by the dominance hierarchy of male determinant alleles through homology-based interactions between sRNAs and target sites. The molecular mechanism underlying the dominance hierarchy in this plant family is likely conserved across species.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Senxu Lu, Xiangyu Ding, Yuanhe Wang, Xiaoyun Hu, Tong Sun, Minjie Wei, Xiaobin Wang, Huizhe Wu
Summary: Recent research suggests that ncRNAs, including miRNA, circRNA, and lncRNAs, are crucial in the development of CRC, with m(6)A methylation playing a key role in ncRNA metabolism. The interaction regulation network among ncRNAs and m(6)A-related regulators remains underexplored, particularly in the context of CRC. Understanding these interactions could provide insights for potential biomarkers and therapeutic targets for improving CRC diagnostic precision and treatment.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Green & Sustainable Science & Technology
Ana Raquel Nunes
Summary: This study investigates the interactions between the sustainable development goals (SDGs) and heatwave resilience, revealing that synergies outweigh trade-offs and there is broad compatibility between the two agendas. However, the analysis also highlights the lack of consistent alignment between the two agendas. Integrated approaches are needed to enhance synergies and achieve both agendas effectively.
ENVIRONMENT DEVELOPMENT AND SUSTAINABILITY
(2023)
Article
Multidisciplinary Sciences
Ci Fu, Xiang Zhang, Amanda O. Veri, Kali R. Iyer, Emma Lash, Alice Xue, Huijuan Yan, Nicole M. Revie, Cassandra Wong, Zhen-Yuan Lin, Elizabeth J. Polvi, Sean D. Liston, Benjamin VanderSluis, Jing Hou, Yoko Yashiroda, Anne-Claude Gingras, Charles Boone, Teresa R. O'Meara, Matthew J. O'Meara, Suzanne Noble, Nicole Robbins, Chad L. Myers, Leah E. Cowen
Summary: Researchers used a machine learning model and chemogenomic analyses to predict genome-wide gene essentiality for the fungal pathogen Candida albicans, and identified the target of a new antifungal compound.
NATURE COMMUNICATIONS
(2021)
Article
Biology
Hossein Lanjanian, Sajjad Nematzadeh, Shadi Hosseini, Mahsa Torkamanian-Afshar, Farzad Kiani, Maryam Moazzam-Jazi, Nizamettin Aydin, Ali Masoudi-Nejad
Summary: RNA-protein interactions of a virus are crucial for the replication of RNA viruses, and a computational study on predicting protein sequence affinity found that key viral proteins are conserved while undesired interactions are pruned. A non-coding RNA identified through high-throughput analysis could serve as a potential drug candidate for NSP5 inhibition.
COMPUTERS IN BIOLOGY AND MEDICINE
(2021)
Article
Neurosciences
Angel K. Kenkpen, Emma R. Olson, Ty E. Guden, Tate T. Card, Ashley S. Jensen, Jordyn L. Ahrens, Rachel A. Hellmann Whitaker
Summary: This study biochemically characterized LINC00298 RNA and elucidated its role in Alzheimer's disease pathogenesis. Through analysis of its protein binding partners, it was determined that LINC00298 RNA may play significant roles in neuronal development, proliferation, and cellular organization.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Biochemical Research Methods
Song Zhang, Kuerbannisha Amahong, Chenyang Zhang, Fengcheng Li, Jianqing Gao, Yunqing Qiu, Feng Zhu
Summary: This study demonstrates that the genomic RNA of SARS-CoV-2 can absorb host miRNAs that regulate immune-related genes, suggesting that this may be a crucial mechanism for the virus to survive and develop in the host. By analyzing miRNA datasets and identifying enriched immune-related pathways and protein-protein interactions, the study reveals an imbalance in the host immune response caused by the absorption of SARS-CoV-2 to host miRNAs, with implications for infection and pathogenesis. Additionally, the study finds that the absorption of host miRNAs by SARS-CoV-2 may contribute to the increased infectivity and pathogenicity of certain mutant strains.
BRIEFINGS IN BIOINFORMATICS
(2022)
Editorial Material
Biochemistry & Molecular Biology
Xiaodong Zhang, Tom Blundell, John A. Tainer
PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY
(2021)
Article
Biology
Hou-Fu Guo, Neus Bota-Rabassedas, Masahiko Terajima, B. Leticia Rodriguez, Don L. Gibbons, Yulong Chen, Priyam Banerjee, Chi-Lin Tsai, Xiaochao Tan, Xin Liu, Jiang Yu, Michal Tokmina-Roszyk, Roma Stawikowska, Gregg B. Fields, Mitchell D. Miller, Xiaoyan Wang, Juhoon Lee, Kevin N. Dalby, Chad J. Creighton, George N. Phillips, John A. Tainer, Mitsuo Yamauchi, Jonathan M. Kurie
Summary: Guo et al. have determined the molecular basis of collagen lysyl hydroxylase 2 (LH2) substrate specificity, showing that LH2 functions not only as a telopeptidyl lysyl hydroxylase, but also as a collagen glucosyltransferase to drive lung cancer progression. The research suggests that LH2 plays a crucial role in promoting LUAD progression through a variety of mechanisms, including tLH-dependent and tLH-independent pathways.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ishtiaque Rashid, Michal Hammel, Aleksandr Sverzhinsky, Miaw-Sheue Tsai, John M. Pascal, John A. Tainer, Alan E. Tomkinson
Summary: TDP1 and LigIII alpha function as key enzymes in single-strand break repair, forming a stable complex for efficient correction of repair defects. Their direct interaction is regulated by phosphorylation and alterations in amino acid sequence, providing insights into a crucial repair pathway in nonmalignant and cancer cells.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Shashank Hambarde, Chi-Lin Tsai, Raj K. Pandita, Albino Bacolla, Anirban Maitra, Vijay Charaka, Clayton R. Hunt, Rakesh Kumar, Oliver Limbo, Remy Le Meur, Walter J. Chazin, Susan E. Tsutakawa, Paul Russell, Katharina Schlacher, Tej K. Pandita, John A. Tainer
Summary: The study reveals the critical role of ATR kinase, BLM helicase, and EXO5 nuclease in coordinating DNA replication fork restart, contributing to cell survival and genomic stability. Elevated EXO5 levels in tumors may lead to increased mutation loads and decreased patient survival rates.
Review
Biochemistry & Molecular Biology
Michal Hammel, John A. Tainer
Summary: NHEJ plays crucial roles in human cells, influencing cancer treatments, antibody diversity, and immune responses to RNA viruses. Advanced SAXS techniques, combined with MX and cryo-EM, provide mechanistic insights into NHEJ structural biochemistry. Integrated structures define dynamic assemblies fundamental for designing mutant variants and allosteric inhibitors.
Article
Genetics & Heredity
Mengling Qi, Peter D. Stenson, Edward Ball, John A. Tainer, Albino Bacolla, Hildegard Kehrer-Sawatzki, David N. Cooper, Huiying Zhao
Summary: Microdeletions and gross deletions are important causes of human inherited disease, and their genomic locations are influenced by the DNA sequence environment. This study analyzed the DNA sequences near breakpoint junctions and found correlations between the frequencies of non-B DNA-forming repeats, GC-content, specific sequence motifs, and deletion length. The study also proposed using a deletion length cut-off of 25-30 bp to functionally distinguish microdeletions from gross deletions.
Article
Biochemistry & Molecular Biology
Susan E. Tsutakawa, Albino Bacolla, Panagiotis Katsonis, Amer Bralic, Samir M. Hamdan, Olivier Lichtarge, John A. Tainer, Chi-Lin Tsai
Summary: The study focuses on decoding unknown significance variants in tumor DNA mutations and their potential impact on clinical treatments. By mapping cancer sequence data and evolutionary trace scores onto structures and utilizing evolutionary action measures, the research highlights the importance of understanding the severity and implications of these mutations. The analysis also reveals insights into the relationship between gene overexpression, functional interactions, and pathways in cancer development, challenging traditional mutation paradigms and emphasizing the need for personalized medicine approaches.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Oncology
Xiangliang Yuan, Yimin Duan, Yi Xiao, Kai Sun, Yutao Qi, Yuan Zhang, Zamal Ahmed, Davide Moiani, Jun Yao, Hongzhong Li, Lin Zhang, Arseniy E. Yuzhalin, Ping Li, Chenyu Zhang, Akosua Badu-Nkansah, Yohei Saito, Xianghua Liu, Wen-Ling Kuo, Haoqiang Ying, Shao-Cong Sun, Jenny C. Chang, John A. Tainer, Dihua Yu
Summary: The study found that vitamin E has a significant impact on the survival rate of patients treated with immune checkpoint therapy, enhancing the efficacy of ICT and promoting antigen presentation by inhibiting SHP1 to activate anti-tumor T-cell immunity.
Article
Cell Biology
Alexandra Berroyer, Albino Bacolla, John A. Tainer, Nayun Kim
Summary: Top1 plays a critical role in maintaining stability at G4-forming genomic loci, and its inhibition by anticancer drugs can lead to increased genomic instability. CPT-resistant Top1 mutants enhance G4-induced recombination and synergize with Nsr1 to exacerbate genomic instability, complicating patient treatment.
Article
Microbiology
Lindsey Spiegelman, Adrian Bahn-Suh, Elizabeth Montano, Ling E. Zhang, Greg Hura, Kathryn M. Patras, Amit Kumar, F. Akif M. Tezcan, Victor Nizet, Susan M. Tsutakawa, Partho Ghosh
Summary: Enterococcus faecalis, a bacterium that can cause hospital-acquired infections, has a protein called Esp that strengthens biofilms by forming amyloid-like fibrils in acidic conditions. This protein increases the retention of Enterococcus within biofilms, contributing to the virulence of the bacterium.
Article
Biochemistry & Molecular Biology
Amer Bralic, Muhammad Tehseen, Mohamed A. Sobhy, Chi-Lin Tsai, Lubna Alhudhali, Gang Yi, Jina Yu, Chunli Yan, Ivaylo Ivanov, Susan E. Tsutakawa, John A. Tainer, Samir M. Hamdan
Summary: Nucleotide excision repair (NER) is crucial for removing bulky DNA lesions, and this study reveals that the XPG nuclease plays a dual role in lesion recognition and excision. XPG stimulates TFIIH-dependent dsDNA unwinding and cleavage activity, and this coordination requires a DNA bubble longer than 15 nucleotides.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Anatomy & Morphology
Valerie S. LeBleu, Jianli Dai, Susan Tsutakawa, Brian A. MacDonald, Joseph L. Alge, Malin Sund, Liang Xie, Hikaru Sugimoto, John Tainer, Leonard I. Zon, Raghu Kalluri
Summary: This study reports on the molecular evolution of type IV collagen genes, finding that the zebrafish a4 non-collagenous (NC1) domain has a cysteine residue and lacks certain residues involved in bond formation between adjacent protomers, potentially affecting its interactions with other chains. The zebrafish a3 NC1 domain exhibits conserved antiangiogenic activity in human endothelial cells despite differences between zebrafish and human versions.
DEVELOPMENTAL DYNAMICS
(2023)
Review
Biochemistry & Molecular Biology
Atanu Mondal, Apoorva Bhattacharya, Vipin Singh, Shruti Pandita, Albino Bacolla, Raj K. Pandita, John A. Tainer, Kenneth S. Ramos, Tej K. Pandita, Chandrima Das
Summary: From initiation to progression, cancer cells experience a variety of internal and external stresses, leading to changes in their epigenome and transcriptome. Understanding the stress response pathways of cancer cells is crucial for developing novel anticancer therapies.
MOLECULAR AND CELLULAR BIOLOGY
(2022)
Article
Oncology
Jia Zhou, Camille Gelot, Constantia Pantelidou, Adam Li, Hatice Yucel, Rachel E. Davis, Anniina Farkkila, Bose Kochupurakkal, Aleem Syed, Geoffrey Shapiro, John A. Tainer, Brian S. J. Blagg, Raphael Ceccaldi, Alan D. D'Andrea
Summary: The antibiotic novobiocin has been identified as a specific POLQ inhibitor with preclinical activity in homologous-recombination-deficient breast and ovarian tumors, including those with acquired PARP inhibitor resistance. This study suggests that novobiocin may be useful alone or in combination with PARP inhibitors for treating HR-deficient tumors.