Review
Genetics & Heredity
Elva Vidya, Thomas F. Duchaine
Summary: This review discusses the regulation of the decapping process, including the roles and assembly of decapping co-factors, the functional convergence of decapping machineries with other RNA-protein complexes, and the models of decapping activation. The complexity of decapping regulation has been revealed through studies, but there are still important gaps to be filled.
FRONTIERS IN GENETICS
(2022)
Review
Biochemistry & Molecular Biology
Fivos Borbolis, Popi Syntichaki
Summary: This article discusses the relationship between mRNA steady-state levels and transcription rate, focusing on the decapping mechanism in post-transcriptional processes. It delves into the role and regulation of decapping enzymes in the mRNA decay pathway, as well as factors that influence their activity.
Article
Biochemistry & Molecular Biology
Christina Krempl, Jan Philip Wurm, Markus Beck Erlach, Werner Kremer, Remco Sprangers
Summary: The study reveals that the Dcp1:Dcp2 mRNA decapping complex undergoes volume changes between its closed and open conformations, which are influenced by ATP.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Izwan Bharudin, Mark X. Caddick, Sean R. Connell, Matthew T. F. Lamaudiere, Igor Y. Morozov
Summary: There are multiple RNA degradation mechanisms in eukaryotes, with mRNA decapping being key. NMD, a process involved in mRNA decapping, is common among eukaryotes. We found that Aspergillus nidulans decapping factors are not required for NMD, unlike in Saccharomyces cerevisiae. Interestingly, disrupting one decapping factor, Dcp1, leads to aberrant ribosome profiles and accumulation of 25S rRNA degradation intermediates.
MOLECULAR MICROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ryan W. Tibble, Anais Depaix, Joanna Kowalska, Jacek Jemielity, John D. Gross
Summary: The activity of Dcp1/Dcp2 in condensates is modulated by interactions promoting phase separation. Dcp1/Dcp2 phase separation stabilizes an inactive conformation in Dcp2 to inhibit decapping, while the activator Edc3 causes a conformational change in Dcp2 to stimulate decapping in condensates. Disruption of the inactive conformation dysregulates decapping in condensates, indicating that enzymatic activity in condensates is regulated across length scales.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Donald. B. B. Bloch, Claire. O. O. Sinow, Andrew. J. J. Sauer, Benjamin H. P. Corman
Summary: In this study, the interactions between components of P-bodies were investigated using a fluorescence-based two-hybrid assay. It was found that LSm14a, PATL1, XRN1, and NBDY interact with the N-terminal portion of EDC4, which contains WD40 domains. The N-terminus of PATL1 mediates the interaction between EDC4 and DDX6.
Article
Biochemistry & Molecular Biology
William R. Brothers, Farah Ali, Sam Kajjo, Marc R. Fabian
Summary: The interaction between XRN1 and EDC4 regulates P-body dynamics to properly coordinate mRNA decapping with 5'-3' decay in human cells. Disrupting this interaction or altering their stoichiometry inhibits mRNA decapping and leads to larger P-bodies. P-bodies support cell viability and prevent stress granule formation when XRN1 is limiting.
Article
Biochemistry & Molecular Biology
Jake C. Swartzel, Michael J. Bond, Andreas P. Pintado-Urbanc, Mehana Daftary, Mackenzie W. Krone, Todd Douglas, Evan J. Carder, Joshua T. Zimmer, Takahiro Maeda, Matthew D. Simon, Craig M. Crews
Summary: The RNA decapping scavenger protein DcpS has been identified as a dependency in acute myeloid leukemia (AML), and its inhibition or knockdown shows antiproliferative effects on AML cells. The non-essential nature of DcpS in normal human hematopoietic cells suggests potential for therapeutic intervention in AML by modulating DcpS activity. JCS-1, a PROTAC developed in this study, effectively degrades DcpS in nanomolar concentrations, offering a new strategy for AML and other DcpS-dependent genetic disorders.
ACS CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Marcelina Bednarczyk, Jessica K. Peters, Renata Kasprzyk, Jagoda Starek, Marcin Warminski, Tomasz Spiewla, Jeffrey S. Mugridge, John D. Gross, Jacek Jemielity, Joanna Kowalska
Summary: Several compounds were identified as inhibitors of VACV D9 decapping enzyme, with m(7)GpppCH(2)p as the most potent nucleotide inhibitor and selicidib and CP-100356 as the most potent drug-like compounds. The identified compounds efficiently inhibited D9 catalyzed decapping of 26 nt RNA substrates but showed no activity towards VACV D10 or human decapping enzyme, Dcp1/2.
ACS CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Christina Krempl, Remco Sprangers
Summary: Nuclear magnetic resonance (NMR) spectroscopy is a powerful tool for studying the dynamics of biomolecules. Fluorine atoms can be used as sensitive probes, but their motions may differ from the backbone motions, highlighting the importance of careful interpretation of fluorine relaxation data.
JOURNAL OF BIOMOLECULAR NMR
(2023)
Review
Biochemistry & Molecular Biology
Feng He, Allan Jacobson
Summary: Decapping is an enzymatic process that removes the 5' cap structures from mRNAs in eukaryotic cells, leading to mRNA degradation. In yeast, mRNA decapping is carried out by a specific decapping enzyme and regulated by decapping activators. This process plays a crucial role in controlling mRNA stability and turnover in various degradation pathways.
Article
Biochemistry & Molecular Biology
Anil Kumar Vijjamarri, Neha Gupta, Chisom Onu, Xiao Niu, Fan Zhang, Rakesh Kumar, Zhenguo Lin, Miriam L. Greenberg, Alan G. Hinnebusch
Summary: We investigated the roles of Pat1 and Dhh1 in regulating mRNA translation and abundance in yeast cells under nutrient-replete conditions. Our findings suggest that Pat1 and Dhh1 cooperatively repress the expression of numerous non-ESR transcripts by reducing decapping and transcription in wild-type cells. Furthermore, we observed impaired mRNA turnover in mutants lacking Dhh1 or Pat1, leading to derepression of these transcripts. Pat1 and Dhh1 also contribute to translational repression and decreased protein production for multiple pathways involved in cell adhesion, nitrogen metabolism, respiration, and autophagy. These findings highlight the post-transcriptional regulatory functions of Pat1 and Dhh1 during nutrient limitation.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Susanne Kramer, Natalia Katarzyna Karolak, Johanna Odenwald, Bernardo Gabiatti, Paula Andrea Castaneda Londono, Anna Zavrelova, Eden Ribeiro Freire, Kayo Schemiko Almeida, Silke Braune, Claudia Moreira, Amelie Eder, Carina Goos, Mark Field, Mark Carrington, Fabiola Holetz, Maria Wiktoria Gorna, Martin Zoltner
Summary: The removal of the mRNA 5' cap is essential for controlling gene expression in eukaryotes. Unlike other eukaryotes, kinetoplastida rely on a unique complex involving ALPH1, XRNA, and other proteins for decapping. This complex has a specific and dynamic localization at the posterior pole of the cell. This unique composition sets the trypanosome decapping complex apart from other eukaryotes.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Neurosciences
Iva Salamon, Geeta Palsule, Xiaobing Luo, Alfonso Roque, Shawn Tucai, Ishan Khosla, Nicole Volk, Wendy Liu, Huijuan Cui, Valentina Dal Pozzo, Petronio Zalamea, Xinfu Jiao, Gabriella D'Arcangelo, Ronald P. Hart, Mladen-Roko Rasin, Megerditch Kiledjian
Summary: Mutations in the gene encoding the scavenger mRNA-decapping enzyme DcpS have been linked to developmental delay and intellectual disability, affecting neuronal differentiation and neurite outgrowth in both human and mouse models. These findings suggest that DcpS plays a crucial role in neural development and further support the association between mRNA metabolism, neocortical pathologies, and intellectual disability.
Article
Biochemistry & Molecular Biology
Vinay K. Nagarajan, Catherine J. Stuart, Anna T. DiBattista, Monica Accerbi, Jeffrey L. Caplan, Pamela J. Green
Summary: In plants, cytoplasmic mRNA decay controlled by DNE1 is crucial for gene expression and RNA homeostasis. Using RNA degradome approaches, this study identified over 200 DNE1 substrates, primarily cleaved within coding regions. While most DNE1 targets were NMD-insensitive, some were NMD-sensitive, indicating its role in turnover of diverse mRNAs. Mutations in the endoribonuclease domain of DNE1 abolished the cleavage, demonstrating its requirement for activity. This work provides important insights into DNE1-mediated mRNA decay.
Article
Biochemistry & Molecular Biology
Stacy L. Erickson, Elizabeth O. Corpuz, Jeffrey P. Maloy, Christy Fillman, Kristofer Webb, Eric J. Bennett, Jens Lykke-Andersen
MOLECULAR AND CELLULAR BIOLOGY
(2015)
Article
Biochemistry & Molecular Biology
Suzanne R. Lee, Gabriel A. Pratt, Fernando J. Martinez, Gene W. Yeo, Jens Lykke-Andersen
Article
Biochemistry & Molecular Biology
Ying Wang, Marc Arribas-Layton, Yifang Chen, Jens Lykke-Andersen, George L. Sen
Article
Biochemistry & Molecular Biology
Kalodiah G. Toma, Indrani Rebbapragada, Sebastien Durand, Jens Lykke-Andersen
Article
Biology
Melissa A. Hausburg, Jason D. Doles, Sandra L. Clement, Adam B. Cadwallader, Monica N. Hall, Perry J. Blackshear, Jens Lykke-Andersen, Bradley B. Olwin
Article
Biochemistry & Molecular Biology
Marcos Arribas-Layton, Jaclyn Dennis, Eric J. Bennett, Christian K. Damgaard, Jens Lykke-Andersen
MOLECULAR AND CELLULAR BIOLOGY
(2016)
Article
Biochemistry & Molecular Biology
Nadia G. D'Lima, Jiao Ma, Lauren Winkler, Qian Chu, Ken H. Loh, Elizabeth O. Corpuz, Bogdan A. Budnik, Jens Lykke-Andersen, Alan Saghatelian, Sarah A. Slavoff
NATURE CHEMICAL BIOLOGY
(2017)
Article
Neurosciences
Fernando J. Martinez, Gabriel A. Pratt, Eric L. Van Nostrand, Ranjan Batra, Stephanie C. Huelga, Katannya Kapeli, Peter Freese, Seung J. Chun, Karen Ling, Chelsea Gelboin-Burkhart, Layla Fijany, Harrison C. Wang, Julia K. Nussbacher, Sara M. Broski, Hong Joo Kim, Rea Lardelli, Balaji Sundararaman, John P. Donohue, Ashkan Javaherian, Jens Lykke-Andersen, Steven Finkbeiner, C. Frank Bennett, Manuel Ares, Christopher B. Burge, J. Paul Taylor, Frank Rigo, Gene W. Yeo
Article
Biochemistry & Molecular Biology
Rui Fu, Myanna T. Olsen, Kristofor Webb, Eric J. Bennett, Jens Lykke-Andersen
Article
Multidisciplinary Sciences
Sebastien Durand, Tobias M. Franks, Jens Lykke-Andersen
NATURE COMMUNICATIONS
(2016)
Article
Genetics & Heredity
Rea M. Lardelli, Ashleigh E. Schaffer, Veerle R. C. Eggens, Maha S. Zaki, Stephanie Grainger, Shashank Sathe, Eric L. Van Nostrand, Zinayida Schlachetzki, Basak Rosti, Naiara Akizu, Eric Scott, Jennifer L. Silhavy, Laura Dean Heckman, Rasim Ozgur Rosti, Esra Dikoglu, Anne Gregor, Alicia Guemez-Gamboa, Damir Musaev, Rohit Mande, Ari Widjaja, Tim L. Shaw, Sebastian Markmiller, Isaac Marin-Valencia, Justin H. Davies, Linda de Meirleir, Hulya Kayserili, Umut Altunoglu, Mary Louise Freckmann, Linda Warwick, David Chitayat, Susan Blaser, Ahmet Okay Caglayan, Kaya Bilguvar, Huseyin Per, Christina Fagerberg, Henrik T. Christesen, Maria Kibaek, Kimberly A. Aldinger, David Manchester, Naomichi Matsumoto, Kazuhiro Muramatsu, Hirotomo Saitsu, Masaaki Shiina, Kazuhiro Ogata, Nicola Foulds, William B. Dobyns, Neil C. Chi, David Traver, Luigina Spaccini, Stefania Maria Bova, Stacey B. Gabrie, Murat Gunel, Enza Maria Valente, Marie-Cecile Nassogne, Eric J. Bennett, Gene W. Yeo, Frank Baas, Jens Lykke-Andersen, Joseph G. Gleeson
Article
Cell Biology
Jennifer N. Chousal, Kyucheol Cho, Madhuvanthi Ramaiah, David Skarbrevik, Sergio Mora-Castilla, Deborah J. Stumpo, Jens Lykke-Andersen, Louise C. Laurent, Perry J. Blackshear, Miles F. Wilkinson, Heidi Cook-Andersen
DEVELOPMENTAL CELL
(2018)
Review
Cell Biology
Jens Lykke-Andersen, Eric J. Bennett
JOURNAL OF CELL BIOLOGY
(2014)
Article
Multidisciplinary Sciences
Boris Reznik, Sandra L. Clement, Jens Lykke-Andersen
Article
Biochemistry & Molecular Biology
Alberto Carreno, Jens Lykke-Andersen
Summary: This study investigates the regulation of mRNA decay activator TTP by the p38 MAPK-MK2 pathway. The results show that the UP CIM recruits the CCR4-NOT deadenylase complex and activates mRNA degradation cooperatively with the conserved tryptophan residues of UP. Interestingly, the UP CIM remains unphosphorylated and can still promote association with the CCR4-NOT complex and mRNA decay upon activation of the p38-MAPK-activated kinase MK2.
MOLECULAR AND CELLULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Damien Marchese, Florent Guislain, Tamara Pringels, Laure Bridoux
Summary: Homopolymeric amino acid repeats are common in human proteins, particularly in transcription factors and kinases. This study focuses on homopolymeric histidine repeats (polyH) and their role in regulating embryonic development. Through bioinformatic analysis, the study identifies that polyH-containing proteins interact with cysteine-rich proteins and proteins containing cysteine repeats. The study further investigates the HOXA1 protein, a transcription factor with a long polyH motif, and finds that the polyH motif is necessary for its interaction with cysteine-rich proteins. Additionally, the study discovers that metal ions are required for the HOXA1-MDFI interaction and identifies three polyH interactors that down-regulate the transcriptional activity of HOXA1.
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
(2024)