Article
Multidisciplinary Sciences
Amit K. Singh, Qingrong Chen, Cu Nguyen, Daoud Meerzaman, Dinah S. Singer
Summary: Cohesin plays a role in regulating alternative splicing by interacting with splicing factors and influencing splicing patterns. Mutations in cohesin are associated with distinct splicing patterns in acute myeloid leukemia, and cohesin interacts with another splicing regulator, BRD4, to generate unique splicing patterns. These findings provide insights into the role of cohesin in both normal and leukemic cells and its contribution to human disease.
Article
Biochemistry & Molecular Biology
Dawid Owsian, Julita Gruchota, Olivier Arnaiz, Jacek K. Nowak
Summary: The study investigates the role of the Spt4-Spt5 complex in non-coding transcription and genome rearrangements using Paramecium tetraurelia as a model organism. The results show that Spt4 is essential for the expression of the germline genome and necessary for developmental genome rearrangements. Silencing of SPT4 genes leads to the absence of double-stranded ncRNAs and reduced levels of scnRNAs. Additionally, a germline-specific Spt4-Spt5m complex is found to be necessary for the transfer of the scnRNA-binding PIWI protein between the germline and somatic nucleus.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Tyler K. Fenstermaker, Svetlana Petruk, Sina K. Kovermann, Hugh W. Brock, Alexander Mazo
Summary: During DNA replication, the transcriptional machinery is believed to dissociate from DNA. However, our study shows that immediately after replication, Pol II, together with other general transcription proteins and immature RNA, re-associates with active genes on both leading and lagging strands of nascent DNA, and rapidly resumes transcription. This suggests that epigenetic marks may not be required for the recruitment of Pol II to newly synthesized DNA during the transition from replication to transcription.
Article
Cell Biology
Elena A. Matveeva, Hejer Dhahri, Yvonne Fondufe-Mittendorf
Summary: The elongation of RNA polymerase along the gene body is tightly regulated, and PARP1 has been shown to regulate it by binding to IntS3. The physical presence of PARP1 affects the recruitment of IntS3 and other elongation factors, rather than its PARylation activity.
Article
Biochemistry & Molecular Biology
Shuaikun Su, Yutong Xue, Alexei Sharov, Yongqing Zhang, Seung Kyu Lee, Jennifer L. Martindale, Wen Li, Wai Lim Ku, Keji Zhao, Supriyo De, Weiping Shen, Payel Sen, Myriam Gorospe, Dongyi Xu, Weidong Wang
Summary: This study investigates the post-transcriptional influence of topoisomerase 3 beta (TOP3B) and associated proteins on mRNA translation and turnover. The findings suggest that TOP3B and TDRD3 have a stronger coordination in mRNA regulation compared to FMRP. The study also reveals that TOP3B can stabilize a subset of target mRNAs and has a complex effect on mRNA translation, which is partly linked to its ability to change the topology of mRNAs.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Chenghao Guo, Yadi Zhang, Shimin Shuai, Abire Sigbessia, Shaohua Hao, Peng Xie, Xu Jiang, Zhuojuan Luo, Chengqi Lin
Summary: In this study, it was found that the regulator SPT5 undergoes phase transition during pause release and is required for gene activation. The super elongation complex (SEC) induces the transition of SPT5 into elongation droplets during early elongation. Mutations in SEC impair the phase properties of elongation droplets and transcription. These findings suggest that SEC-mediated SPT5 phase transition is essential for pause release and early elongation, and aberrant phase properties may contribute to transcription abnormalities in diseases.
Article
Biochemistry & Molecular Biology
Junaid Akhtar, Yoan Renaud, Steffen Albrecht, Yad Ghavi-Helm, Jean-Yves Roignant, Marion Silies, Guillaume Junion
Summary: m(6)A RNA modification regulates RNAP II pausing in Drosophila cells, affecting pause release, Ser2P occupancy, and nascent RNA transcription. The m(6)A-mediated gene regulation adds another layer to the control of gene expression.
Article
Multidisciplinary Sciences
Dominik Muehlen, Xiaojuan Li, Oleksandr Dovgusha, Herbert Jaeckle, Ufuk Guenesdogan
Summary: Epigenetic inheritance during DNA replication requires the assembly of nucleosomes from parental and newly synthesized histones. Lack of new histone synthesis leads to accessible chromatin, reduced nucleosome occupancy, and up-regulated and spurious transcription. However, the positions of modified parental histones are largely restored during DNA replication, suggesting recycling of parental histones to preserve the epigenetic landscape.
Article
Multidisciplinary Sciences
Mara De Marco Zompit, Monica Torres Esteban, Clemence Mooser, Salome Adam, Silvia Emma Rossi, Alain Jeanrenaud, Pia-Amata Leimbacher, Daniel Fink, Ann-Marie K. Shorrocks, Andrew N. Blackford, Daniel Durocher, Manuel Stucki
Summary: In this study, CIP2A is identified as a protein that interacts with TOPBP1 and specifically regulates its localization in mitosis. Cells lacking CIP2A show increased radio-sensitivity, micronuclei formation, and chromosomal instability.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Li Ding, Maciej Paszkowski-Rogacz, Jovan Mircetic, Debojyoti Chakraborty, Frank Buchholz
Summary: Paf1C positively regulates enhancer activity in mouse embryonic stem cells, with extensive presence and function at super enhancers; Paf1C occupancy correlates with the strength of enhancer activity, improving the predictive power for classifying enhancers in genomic sequences; Depletion of Paf1C affects the expression of genes regulated by targeted enhancers, indicating its crucial role in maintaining mouse embryonic stem cell self-renewal.
LIFE SCIENCE ALLIANCE
(2021)
Article
Multidisciplinary Sciences
Anne E. Roehrig, Kristina Klupsch, Juan A. Oses-Prieto, Selim Chaib, Stephen Henderson, Warren Emmett, Lucy C. Young, Silvia Surinova, Andreas Blees, Anett Pfeiffer, Maha Tijani, Fabian Brunk, Nicole Hartig, Marta Munoz-Alegre, Alexander Hergovich, Barbara H. Jennings, Alma L. Burlingame, Pablo Rodriguez-Viciana
Summary: The study investigates the roles of the PAF complex and Merlin tumor suppressor protein in RNA processing, highlighting their interaction for growth suppression. Additionally, the involvement of FAT cadherins in regulating Merlin-PAFC interaction is identified as a significant finding from the research.
Article
Biochemistry & Molecular Biology
Shyam Ramasamy, Abrar Aljahani, Magdalena A. Karpinska, T. B. Ngoc Cao, Taras Velychko, J. Neos Cruz, Michael Lidschreiber, A. Marieke Oudelaar
Summary: The authors conducted a study to investigate the role of the Mediator complex in the regulation of enhancer-promoter interactions. They found that depletion of Mediator led to a reduction in enhancer-promoter interaction frequencies and gene expression, as well as an increase in interactions between CTCF-binding sites. These changes in chromatin architecture were associated with a redistribution of the Cohesin complex on chromatin and a decreased Cohesin occupancy at enhancers. Overall, this study provides insights into the molecular mechanisms of communication between enhancers and promoters.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
How-Wing Leung, Gabriel Wei Quan Foo, Antonius M. J. VanDongen
Summary: The immediate early gene Arc plays a crucial role in regulating synaptic function and memory consolidation. It interacts with dynamic chromatin and associates with histone markers for active enhancers and transcription in cultured rat hippocampal neurons. Upregulated histone modifications associated with late-onset Alzheimer's disease have been found. Altered expression profiles of over 1900 genes, including those involved in synaptic function, neuronal plasticity, excitability, and signaling pathways, were observed when Arc induction was prevented. About 100 Arc-dependent genes are implicated in the pathophysiology of Alzheimer's disease. The induction of endogenous Arc expression in HEK293T cells increased the transcription of neuronal genes, suggesting that Arc can control gene expression independently of activated signaling pathways. These findings establish Arc as a master regulator of activity-dependent gene expression in neurons and suggest its significance in Alzheimer's disease pathophysiology.
Article
Biochemistry & Molecular Biology
Kirsten A. Reimer, Claudia A. Mimoso, Karen Adelman, Karla M. Neugebauer
Summary: The study revealed tight coordination between co-transcriptional splicing and transcription elongation and 3' end formation in mammalian cells, with splicing delays possibly taking place between the two catalytic steps. Additionally, inefficient 3' end cleavage was associated with intron retention, highlighting the functional coupling between these co-transcriptional processes.
Article
Multidisciplinary Sciences
Haruhiko Ehara, Tomoya Kujirai, Mikako Shirouzu, Hitoshi Kurumizaka, Shun-ichi Sekine
Summary: This study used cryo-electron microscopy to obtain structures of RNA polymerase II (RNAPII) passing through nucleosomes during gene transcription. The researchers also identified the roles of transcription elongation factors and histone chaperones in nucleosome disassembly and reassembly.
Article
Biochemistry & Molecular Biology
Victoria Begley, Antonio Jordan-Pla, Xenia Penate, Ana Garrido-Godino, Drice Challal, Abel Cuevas-Bermudez, Adria Mitjavila, Mara Barucco, Gabriel Gutierrez, Abhyudai Singh, Paula Alepuz, Francisco Navarro, Domenico Libri, Jose E. Perez-Ortin, Sebastian Chavez
Summary: The study demonstrated significant effects of Xrn1 perturbation on transcription elongation through changes in RNA Pol II profiles and nucleosome mapping in Saccharomyces cerevisiae. Additionally, accumulation of RNA Pol II upstream of polyadenylation sites was detected, suggesting a connection between mRNA decay and late transcription elongation. These findings indicate that Xrn1 influences transcription elongation through multiple mechanisms.
Article
Biochemistry & Molecular Biology
Helena Santos-Rosa, Gonzalo Millan-Zambrano, Namshik Han, Tommaso Leonardi, Marie Klimontova, Simona Nasiscionyte, Luca Pandolfini, Kostantinos Tzelepis, Till Bartke, Tony Kouzarides
Summary: The study reveals that histone H3 lysine 37 mono-methylation plays a crucial role in regulating DNA replication origin licensing, inhibiting the interaction of MCM proteins with chromatin, and maintaining low levels of MCM outside of replication origins.
Article
Cell Biology
Andres Herrero-Ruiz, Pedro Manuel Martinez-Garcia, Jose Terron-Bautista, Gonzalo Millan-Zambrano, Jenna Ariel Lieberman, Silvia Jimeno-Gonzalez, Felipe Cortes-Ledesma
Summary: Contrary to the common assumption, the activity of human topoisomerase II alpha (TOP2A) at promoters represses the transcription of certain immediate early genes, keeping them in a basal repressed state. Inhibition of TOP2A leads to a specific topological context that facilitates rapid release from promoter-proximal pausing and transcriptional upregulation, resembling the bursting behavior of these genes in response to physiological stimuli. Control of promoter-proximal pausing by TOP2A is described as a regulatory layer for gene expression, serving as a molecular switch for rapid transcriptional activation by potentially regulating the accumulation of DNA supercoiling at promoter regions.
Article
Biochemistry & Molecular Biology
Laura Payan-Bravo, Sara Fontalva, Xenia Penate, Ildefonso Cases, Jose Antonio Guerrero-Martinez, Yerma Pareja-Sanchez, Yosu Odriozola-Gil, Esther Lara, Silvia Jimeno-Gonzalez, Carles Sune, Mari Cruz Munoz-Centeno, Jose C. Reyes, Sebastian Chavez
Summary: The study demonstrates that perturbations in prefoldin lead to transcriptional alterations in the human genome, particularly affecting splicing and expression of long genes with a high number of introns.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Jose Garcia-Martinez, Daniel A. Medina, Pablo Bellvis, Mai Sun, Patrick Cramer, Sebastian Chavez, Jose E. Perez-Ortin
Summary: The study found no genetic compensation of NMD mRNA targets in yeast, and total mRNA buffering primarily uses a global system rather than a gene-specific one.
Correction
Oncology
Estefania Garcia-Guerrero, Ralph Gotz, Soren Doose, Markus Sauer, Alfonso Rodriguez-Gil, Thomas Nerreter, K. Martin Kortum, Jose A. Perez-Simon, Hermann Einsele, Michael Hudecek, Sophia Danhof
Review
Genetics & Heredity
Gonzalo Millan-Zambrano, Adam Burton, Andrew J. Bannister, Robert Schneider
Summary: This Review discusses the impact of histone post-translational modifications (PTMs) on DNA processes and emphasizes their role in genome regulation. It explores the different ways in which PTMs can influence DNA-templated processes, such as transcription, recombination, replication, DNA repair, and genomic architecture. The review also highlights important advances in understanding how histone PTMs can exert direct or indirect effects on genome function.
NATURE REVIEWS GENETICS
(2022)
Article
Multidisciplinary Sciences
Alfonso Rodriguez-Gil, Virginia Escamilla-Gomez, Melanie Nufer, Felix Andujar-Sanchez, Teresa Lopes-Ramos, Jose Antonio Bejarano-Garcia, Estefania Garcia-Guerrero, Cristina Calderon-Cabrera, Teresa Caballero-Velazquez, Clara Beatriz Garcia-Calderon, Paola Hernandez-Diaz, Juan Luis Reguera-Ortega, Nancy Rodriguez-Torres, Nuria Martinez-Cibrian, Jose Ignacio Rodriguez-Barbosa, Javier Villadiego, Jose Antonio Perez-Simon
Summary: Donor derived regulatory T lymphocytes and the JAK1/2 kinase inhibitor ruxolitinib are currently being evaluated as therapeutic options in the treatment of chronic graft versus host disease (cGvHD). In this study, the researchers aimed to investigate the combined effect of these two agents in the treatment of GvHD using both in vitro and in vivo models. The results showed that the combination of ruxolitinib and Treg was more effective in reducing GvHD incidence, severity and improving survival compared to each single treatment alone.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Laura Contreras, Alfonso Rodriguez-Gil, Jordi Muntane, Jesus de la Cruz
Summary: Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related mortality worldwide. Sorafenib (Sfb) is the current first-line treatment for advanced HCC, but its therapeutic benefit is limited. This study analyzed the gene expression changes in two liver cancer cell lines upon Sfb treatment and found similar responses in both cell lines. The results provide valuable information on the molecular action of Sfb and suggest potential strategies to improve clinical outcomes.
Review
Biochemistry & Molecular Biology
Alfonso Rodriguez-Gil, Estrella Carrillo-Cruz, Cristina Marrero-Cepeda, Guillermo Rodriguez, Jose A. Perez-Simon
Summary: Vitamin D plays a dual role in the immune system and tumor cells, potentially decreasing graft-versus-host disease and relapse rates.
Article
Biochemistry & Molecular Biology
Jose E. Perez-Ortin, Sebastian Chavez
Summary: Gene expression is a highly regulated process that adapts RNA and protein content to the cellular environment. RBPs can shuttle between the nucleus and cytoplasm to regulate transcription, mRNA degradation, and translation, acting as potential coordinators of mRNA metabolism.
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
(2022)
Meeting Abstract
Hematology
Maria Vd Soares, Virginia Escamilla Gomez, Rita Azevedo, Paulo N. G. Pereira, Teresa Caballero Velazquez, Clara B. Garcia-Calderon, Kukatharmini Tharmaratnam, Ines A. Cabral, Ana C. Ribeiro, Laura Mendes, Clara Juncal, Susana Roncon, Ana Teresa Pais, Ana C. Alho, Alfonso Rodriguez Gil, Eduardo L. Espada, Anabela Rodrigues, Ana Garcao, Marie-Laure Yaspo, Hans-Joerg Warnatz, Hans Lehrach, Nuno L. Barbosa-Morais, Ana Miguel Quintas, Paulo Palmela, Cecilia Caldas, Rosa Ferreira, Luis Leite, Carlos Martins, Fernanda Lourenco, Raul Moreno, Joao Raposo, Fernando Campilho, Christopher Paul Cheyne, Marta Garcia-Finana, Antonio Campos, Frederic Baron, Mario Arpinati, Matthias Edinger, Jerome Ritz, Carlos Pinho Vaz, Jose A. Perez-Simon, Joao F. Lacerda
Article
Biochemistry & Molecular Biology
Jose Garcia-Martinez, Abhyudai Singh, Daniel Medina, Sebastian Chavez, Jose E. Perez-Ortin
Summary: In recent years, it has become increasingly clear that gene expression in eukaryotes is a circular process where mRNA levels are controlled by crosstalk between transcription and mRNA decay pathways. This crosstalk can result in either buffering or enhanced gene expression regulation, depending on whether transcription and mRNA degradation act at compensatory rates or additively. The study shows that certain proteins presumed to be only involved in transcription or mRNA decay may actually be RNA-binding proteins (RBPs) that have specific crosstalk effects, enhancing the control of mRNA levels.
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
(2023)
Editorial Material
Immunology
Alfonso Rodriguez-Gil, Jose A. Perez-Simon, Jerome Ritz, Joao F. Lacerda, Maria VD. Soares
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biology
Victoria Begley, Lola De Miguel-Jimenez, Sebastian Chavez
Summary: DNA transcription by RNA polymerases is a crucial process in genome expression, and scientists utilize various methods like TRO and ChIP to quantify RNA polymerase levels at specific genomic sites. TRO is particularly useful for studying active transcription on a single gene scale by quantifying the signal of transcripts, providing an advantage over other methods that may also measure inactive polymerases.