Article
Biochemistry & Molecular Biology
Yuan Yang, Shihen Liu, Sylvain Egloff, Catherine D. Eichhorn, Tanya Hadjian, James Zhen, Tamas Kiss, Z. Hong Zhou, Juli Feigon
Summary: The study presents the cryo-EM structures of the 7SK core RNP and uncovers the interactions between different components. The mechanism of MePCE catalytic inactivation and the role of Larp7 as an RNP chaperone are revealed. The MePCE-7SK-Larp7 core RNP serves as a scaffold for switching between different 7SK conformations and regulating P-TEFb sequestration and release.
Article
Medicine, Research & Experimental
Shane D. Falcinelli, Jackson J. Peterson, Anne-Marie W. Turner, David Irlbeck, Jenna Read, Samuel L. M. Raines, Katherine S. James, Cameron Sutton, Anthony Sanchez, Ann Emery, Gavin Sampey, Robert Ferris, Brigitte Allard, Simon Ghofrani, Jennifer L. Kirchherr, Caroline Baker, JoAnn D. Kuruc, Cynthia L. Gay, Lindsey I. James, Guoxin Wu, Paul Zuck, Inmaculada Rioja, Rebecca C. Furze, Rab K. Prinjha, Bonnie J. Howell, Ronald Swanstrom, Edward P. Browne, Brian D. Strahl, Richard M. Dunham, Nancie M. Archin, David M. Margolis
Summary: This study demonstrates the synergy in latent reservoir activation when using inhibitor of apoptosis protein (IAP) antagonists in combination with bromodomain and extraterminal domain protein inhibitors (BETi). It also highlights the importance of HIV transcriptional elongation and splicing as barriers to latent HIV protein expression, providing a rationale for further exploration of IAPi+BETi in animal models of HIV latency.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Multidisciplinary Sciences
Marcelo Perez-Pepe, Anthony W. Desotell, Hengyi Li, Wenxue Li, Bing Han, Qishan Lin, Daryl E. Klein, Yansheng Liu, Hani Goodarzi, Claudio R. Alarcon
Summary: A fundamental feature of cell signaling is the conversion of extracellular signals into adaptive transcriptional responses. The role of RNA modifications in this process is poorly understood. We found that epidermal growth factor signaling induces phosphorylation of the enzyme methyltransferase 3 (METTL3), leading to METTL3-mediated methylation of 7SK. 7SK methylation enhances its binding to heterogeneous nuclear ribonucleoproteins, causing the release of the HEXIM1/P-TEFb complex and inducing transcriptional elongation. Our findings establish the mechanism underlying 7SK activation and uncover a previously unknown function for the m6A modification in converting growth factor signaling events into a regulatory transcriptional response via an RNA methylation-dependent switch.
Article
Biochemistry & Molecular Biology
Yuzhi Wang, Conner M. Traugot, Jodi L. Bubenik, Tianqi Li, Peike Sheng, Nicholas M. Hiers, Paul Fernandez, Lu Li, Jiang Bian, Maurice S. Swanson, Mingyi Xie
Summary: This study reveals that N6-methyladenosine modifications on a non-coding RNA, 7SK, play a crucial role in regulating RNA polymerase II transcription in non-small cell lung cancer. The removal of this modification leads to structural rearrangements in 7SK, resulting in the sequestration of positive transcription elongation factor b (P-TEFb) complex and a reduction in RNA polymerase II activity. This finding sheds light on the mechanism of how m6A modifications regulate tumorigenesis in NSCLC.
Article
Biochemistry & Molecular Biology
Rongdiao Liu
Summary: CDK9 is a crucial kinase subunit of P-TEFb that is important for effective transcriptional elongation. The activity of P-TEFb is maintained through dynamic association with larger protein complexes. In this study, we find that CDK9 expression is induced upon inhibition of P-TEFb activity, a process dependent on Brd4. Inhibition of Brd4 synergizes with CDK9 inhibitor to suppress P-TEFb activity and tumor cell growth. Our findings suggest that combined inhibition of Brd4 and CDK9 could be a potential therapeutic strategy.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Samuel W. Olson, Anne-Marie W. Turner, J. Winston Arney, Irfana Saleem, Chase A. Weidmann, David M. Margolis, Kevin M. Weeks, Anthony M. Mustoe
Summary: This study used a single-molecule chemical probing strategy, DANCE-MaP, to define the structural dynamics of 7SK RNA and revealed its role in regulating transcription and responding to cellular signals.
Article
Multidisciplinary Sciences
Sarah M. Lloyd, Daniel B. Leon, Mari O. Brady, Deborah Rodriguez, Madison P. McReynolds, Junghun Kweon, Amy E. Neely, Laura A. Blumensaadt, Patric J. Ho, Xiaomin Bao
Summary: In this study, the researchers found that the Super Elongation Complex (SEC) controls fate decisions of progenitor cells by suppressing a group of rapid response genes. The repressive role of SEC depends on the AFF1 scaffold, but not AFF4. The expression of these rapid response genes is regulated by CDK9 activity. The findings suggest that the activity switch of SEC-associated CDK9 is a key initial process in determining the fate of progenitor cells.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Cecilia Studniarek, Michael Tellier, Pascal G. P. Martin, Shona Murphy, Tamas Kiss, Sylvain Egloff
Summary: The lack of 7SK snRNP has minor impact on global RNAPII transcription under normal conditions, but impairs transcriptional response and reduces viability upon UV-light-induced DNA damage. 7SK is crucial for proper induction of UV-responsive genes and orchestrating the transcriptional response to stress.
Article
Cell Biology
Isaque J. S. de Faria, Eric R. G. R. Aguiar, Roenick P. Olmo, Juliana Alves da Silva, Laurent Daeffler, Richard W. Carthew, Jean-Luc Imler, Joao T. Marques
Summary: dsRNA sensing triggers antiviral responses against RNA and DNA viruses in diverse eukaryotes. In Drosophila, the large DNA virus IIV-6 triggers production of siRNAs by activating Dicer-2, initiating an antiviral immune response.
Article
Biochemistry & Molecular Biology
Kai Zhou, Songkuan Zhuang, Fulong Liu, Yanheng Chen, You Li, Shihui Wang, Yuxuan Li, Huixin Wen, Xiaohua Lin, Jie Wang, Yue Huang, Cailing He, Nan Xu, Zongshu Li, Lang Xu, Zixuan Zhang, Lin-Feng Chen, Ruichuan Chen, Min Liu
Summary: P-TEFb modulates RNA polymerase II elongation through interaction with Brd4 and SEC. This study uncovers a novel mechanism for the reassembly of Cdk9 and CycT1 monomers on chromatin to form active P-TEFb.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Cell Biology
Irene P. Chen, James E. Longbotham, Sarah McMahon, Rahul K. Suryawanshi, Mir M. Khalid, Taha Y. Taha, Takako Tabata, Jennifer M. Hayashi, Frank W. Soveg, Jared Carlson-Stevermer, Meghna Gupta, Meng Yao Zhang, Victor L. Lam, Yang Li, Zanlin Yu, Erron W. Titus, Amy Diallo, Jennifer Oki, Kevin Holden, Nevan Krogan, Danica Galonie Fujimori, Melanie Ott
Summary: Inhibitors of BET proteins, which downregulate ACE2 expression, could be potential prophylactics for SARS-CoV-2. However, it has been found that BET proteins play a critical role as antiviral factors at the post-entry level, suggesting that therapeutic inactivation of BET proteins should be avoided. BET inhibitors exacerbate SARS-CoV-2 infection, viral replication, and mortality, while suppressing interferon production.
Article
Biochemistry & Molecular Biology
Changhe Ji, Chunchu Deng, Katharina Antor, Thorsten Bischler, Cornelius Schneider, Utz Fischer, Michael Sendtner, Michael Briese
Summary: Loss of hnRNP R promotes the release of P-TEFb from 7SK and enhances hnRNP A1 binding to 7SK, indicating the negative regulation of transcription. hnRNP R interacts with BRD4 and its depletion increases BRD4 binding to CDK9. Additionally, CDK9 is stabilized upon loss of hnRNP R and its association with Cyclin K is enhanced.
Review
Cell Biology
Xuepeng Wang, Yudan Fan, Qiang Wu
Summary: Transcription elongation is a crucial molecular process that regulates gene expression and its malfunction can lead to impaired cellular functions. Understanding the regulatory mechanisms of transcription elongation in embryonic stem cells (ESCs) is important for both basic research and clinical applications in regenerative medicine, as ESCs have the potential to differentiate into various cell types.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Physics, Multidisciplinary
Purba Chatterjee, Nigel Goldenfeld, Sangjin Kim
Summary: Recent experiments have shown that mechanical stress associated with transcription can lead to a transition in RNA polymerase group dynamics from cooperative to antagonistic upon promoter repression. A continuum deterministic model for transcription under torsion was developed to elucidate the mechanism behind this transition, successfully reproducing experimental findings and shedding light on the interplay of mechanical and biological factors in the collective dynamics of molecular machines involved in gene expression.
PHYSICAL REVIEW LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Subham Basu, Arijit Nandy, Avik Ghosh, Dheerendra Pratap Mall, Debabrata Biswas
Summary: This study reveals the important role of STUB1 in regulating the overall level of CDK9 and P-TEFb complex. STUB1 acts as a ubiquitin E3 ligase for the proteasomal degradation of CDK9. CyclinT1 protects CDK9 from STUB1-mediated degradation through binding to the same region of CDK9. Knockdown of STUB1 enhances CDK9 expression, leading to increased P-TEFb complex formation and transcriptional activation of diverse target genes.
MOLECULAR AND CELLULAR BIOLOGY
(2023)
Article
Medicine, General & Internal
Ryo Matsumiya, Osamu Hosono, Noritada Yoshikawa, Masaaki Uehara, Hiroshi Kobayashi, Aya Oda, Erika Matsubara, Shuji Tanada, Yukako Shintani, Kazuhiro Nagayama, Jun Nakajima, Hirotoshi Tanaka
Article
Multidisciplinary Sciences
Noriaki Shimizu, Takako Maruyama, Noritada Yoshikawa, Ryo Matsumiya, Yanxia Ma, Naoki Ito, Yuki Tasaka, Akiko Kuribara-Souta, Keishi Miyata, Yuichi Oike, Stefan Berger, Guenther Schuetz, Shin'ichi Takeda, Hirotoshi Tanaka
NATURE COMMUNICATIONS
(2015)
Article
Rheumatology
Noritada Yoshikawa, Noriaki Shimizu, Masaaki Uehara, Aya Oda, Ryo Matsumiya, Erika Matsubara, Hiroshi Kobayashi, Osamu Hosono, Akiko Kuribara-Souta, Hiroyuki Baba, Fumitaka Nagamura, Shigeru Kiryu, Hirotoshi Tanaka
MODERN RHEUMATOLOGY
(2017)
Article
Cell Biology
Noriaki Shimizu, Noritada Yoshikawa, Naoki Ito, Takako Maruyama, Yuko Suzuki, Sin-ichi Takeda, Jun Nakae, Yusuke Tagata, Shinobu Nishitani, Kenji Takehana, Motoaki Sano, Keiichi Fukuda, Makoto Suematsu, Chikao Morimoto, Hirotoshi Tanaka
Meeting Abstract
Cardiac & Cardiovascular Systems
Motoaki Sano, Satori Tokudome, Noriaki Shimizu, Noritada Yoshikawa, Hirotoshi Tanaka, Keiichi Fukuda
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2008)
Article
Rheumatology
Kei Ohnuma, Osamu Hosono, Hiroshi Kawasaki, Noritada Yoshikawa, Tomoki Katayose, Naoki Oyaizu, Hirotoshi Tanaka, Chikao Morimoto
MODERN RHEUMATOLOGY
(2009)
Article
Rheumatology
Osamu Hosono, Noritada Yoshikawa, Noriaki Shimizu, Shigeru Kiryu, Masaaki Uehara, Hiroshi Kobayashi, Ryo Matsumiya, Akiko Kuribara, Takako Maruyama, Hirotoshi Tanaka
MODERN RHEUMATOLOGY
(2015)
Article
Endocrinology & Metabolism
Noriaki Shimizu, Noritada Yoshikawa, Tadashi Wada, Hiroshi Handa, Motoaki Sano, Keiichi Fukuda, Makoto Suematsu, Takashi Sawai, Chikao Morimoto, Hirotoshi Tanaka
MOLECULAR ENDOCRINOLOGY
(2008)
Article
Multidisciplinary Sciences
Noritada Yoshikawa, Noriaki Shimizu, Takako Maruyama, Motoaki Sano, Tomohiro Matsuhashi, Keiichi Fukuda, Masaharu Kataoka, Toru Satoh, Hidenori Ojima, Takashi Sawai, Chikao Morimoto, Akiko Kuribara, Osamu Hosono, Hirotoshi Tanaka
Article
Rheumatology
Kei Ohnuma, Osamu Hosono, Tomoki Katayose, Noritada Yoshikawa, Hiroshi Kawasaki, Takeshi Fujii, Naoki Oyaizu, Hirotoshi Tanaka, Chikao Morimoto
RHEUMATOLOGY INTERNATIONAL
(2010)
Article
Clinical Neurology
Hiroshi Kobayashi, Masaaki Uehara, Aya Oda, Erika Matsubara, Hiroyuki Baba, Ryo Matsumiya, Noritada Yoshikawa, Osamu Hosono, Hirotoshi Tanaka
INTERDISCIPLINARY NEUROSURGERY-ADVANCED TECHNIQUES AND CASE MANAGEMENT
(2016)
Article
Endocrinology & Metabolism
N Yoshikawa, K Yamamoto, N Shimizu, S Yamada, C Morimoto, H Tanaka
MOLECULAR ENDOCRINOLOGY
(2005)
Article
Urology & Nephrology
T Iida, Y Makino, K Okamoto, N Yoshikawa, I Makino, T Nakamura, H Tanaka
KIDNEY INTERNATIONAL
(2000)
Article
Medicine, Research & Experimental
K Migita, H Tanaka, K Okamoto, N Yoshikawa, Y Ichinose, S Urayama, S Yamasaki, H Ida, Y Kawabe, A Kawakami, K Eguchi
LABORATORY INVESTIGATION
(2000)
Article
Biochemistry & Molecular Biology
Soojung Hahn, Gyuri Kim, Sang-Man Jin, Jae Hyeon Kim
Summary: This study utilized three-dimensional intestinal organoids to investigate the effects of metformin on inflammatory bowel disease (IBD) and found that metformin can enhance intestinal barrier function and reduce levels of inflammatory cytokines.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
V. V. Sudarev, M. S. Gette, S. V. Bazhenov, O. M. Tilinova, E. V. Zinovev, I. V. Manukhov, A. I. Kuklin, Yu. L. Ryzhykau, A. V. Vlasov
Summary: This study investigated the self-assembly processes of ferritin-based protein complexes and obtained structurally characterized oligomeric states. These results provide new potential and opportunities for the application of ferritin in various fields.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Yalda Sabaghi, Farnaz Pourfarzad, Leila Zolghadr, Azita Bahrami, Tahereh Shojazadeh, Alireza Farasat, Nematollah Gheibi
Summary: p-Coumaric acid (p-CA) is a plant compound with anti-cancer activities. This study designed a nano-liposomal carrier containing p-CA to enhance its effectiveness against melanoma cells. The findings showed that the liposomal form of p-CA had a greater impact on the cells. Kinetic modeling indicated that the best fitting model was zero-order.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
M. D. Nazmul Hasan, Md Mahfuzur Rahman, Al Asmaul Husna, Nobuhiro Nozaki, Osamu Yamato, Naoki Miura
Summary: This study investigated the expression of ncRNAs other than miRNAs in different histologic subtypes of canine mammary gland tumors (MGT). Three aberrantly expressed ncRNAs were identified as potential biomarkers for differentiating MGT subtypes. YRNA and tRFs expression levels were found to be decreased in metastatic compared to primary MGT cell lines.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Seine A. Shintani
Summary: In this study, the researchers used signal analysis to study the instantaneous amplitude and phase of sarcomeric oscillations in skeletal muscle. They identified two types of oscillations, sarcomeric oscillations and sarcosynced oscillations, and visualized their behavior during propagating waves. The researchers discovered the presence of sarcomeric defect holes and sarcomeric collision holes, which are important indicators for understanding the oscillation properties of sarcomeres. This finding has important implications for improving our understanding of muscle function and its regulatory mechanisms.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Shuanglin Zhang, Yuzhong Jia, Guolan Ma, Yanyan Yang, Zhenzhen Cao, Antao Luo, Zefu Zhang, Shihan Li, Jie Wen, Hanfeng Liu, Jihua Ma
Summary: Bupleurum is an antiarrhythmic agent that may exert its effects by inhibiting L-type calcium channels.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Tomotaka Ohkubo, Yasuhiko Matsumoto, Hiroaki Sasaki, Kaoru Kinoshita, Yuki Ogasawara, Takashi Sugita
Summary: This study found that Citrobacter koseri inhibits the growth of Staphylococcus epidermidis, disrupting the balance between S. epidermidis and Staphylococcus aureus, and exacerbating inflammation in atopic dermatitis.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Toshifumi Asano, Philipp Sasse, Takao Nakata
Summary: A Cre recombination-based fluorescent reporter system was developed to monitor cell-cell fusion. The system successfully detected the formation of multinuclear myotubes and placental syncytiotrophoblast. This tool could facilitate the study of cell-to-cell fusion.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Ke Shi, Yunlong Shan, Xiao Sun, Kuida Chen, Qiong Luo, Qiang Xu
Summary: This study found that low expression of TP53INP2 is associated with poor survival in colorectal cancer (CRC) patients. As the malignancy of CRC progresses, TP53INP2 expression gradually decreases. Knockdown of TP53INP2 promotes CRC cell proliferation and tumor growth. Mechanistically, TP53INP2 deficiency decreases phosphorylation of beta-catenin, leading to increased accumulation and enhanced nuclear translocation and transcriptional activity. Additionally, TP53INP2 sequesters TIM50, inhibiting its activation of beta-catenin. In conclusion, downregulation of TP53INP2 promotes CRC progression by activating beta-catenin.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Martina Rossi, Fabio Tomaselli, Alejandro Hochkoeppler
Summary: Oligomeric enzymes are known for their higher catalytic rates compared to monomeric enzymes, but the extent of additivity in their activity is still not well understood. This study used tetrameric rabbit lactate dehydrogenase as a model to examine the kinetics of its catalytic action. Surprisingly, when the concentration of the limiting reactant exceeded that of a single subunit, there was a significant slowdown in the enzyme's conformational rearrangements.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Amin Sahraei, Mohammad Javad Shamsoddini, Fakhrossadat Mohammadi, Leila Hassani
Summary: This study explored the inhibitory effects of gallium curcumin, indium curcumin, and vanadyl curcumin on the amyloid fibrillation of hen egg white lysozyme, as well as the binding interactions of these metal complexes with the enzyme. The results showed that indium curcumin and vanadyl curcumin exhibited higher binding affinities and stronger inhibitory effects on amyloid fibrillation compared to gallium curcumin.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Takahiro Sasaki, Yoshiki Kuse, Shinsuke Nakamura, Masamitsu Shimazawa
Summary: PGRN deficiency plays a significant role in cardiac remodeling and arrhythmias post-myocardial infarction (MI), potentially by promoting metabolic abnormalities in macrophages.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Hongwei Zhao, Yiqiang Li, Yibo Zhang, Chi Zhang
Summary: Electrical brain stimulation technology is commonly used to treat brain neurological disorders, but it can cause side effects. This study investigated the impact of electric fields on nerve fibers and revealed the possible origin of side effects. The findings provide guidance for selecting electrical parameters in clinical stimulation therapy.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Julia S. Scott, Lake-Ee Quek, Andrew J. Hoy, Johannes V. Swinnen, Zeyad D. Nassar, Lisa M. Butler
Summary: The fatty acid elongation enzyme ELOVL5 plays a critical role in promoting metastasis in prostate cancer. Knocking down ELOVL5 leads to the accumulation of malonyl-CoA, which inhibits fatty acid oxidation in mitochondria. This study highlights the importance of fatty acid elongation in regulating cell viability and provides a potential target for prostate cancer treatment.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Zan Zhou, Wen-jun Jiang, Li Li, Jun-qiang Si
Summary: This study investigates the effect of noise exposure on cognitive function in mice and explores the underlying molecular mechanisms. The findings suggest that noise exposure leads to increased inflammation, increased phosphorylation of Tau protein, and decreased levels of postsynaptic density protein, resulting in cognitive impairment.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)