Review
Biochemical Research Methods
Mattia Furlan, Stefano de Pretis, Mattia Pelizzola
Summary: Despite RNA abundance being commonly assumed as a proxy for transcriptional activity, it is now possible to calculate how synthesis, processing, and degradation rates collectively determine the abundance of each gene's RNA. Different transcriptional outputs can correspond to different combinations of kinetic rates, indicating the existence of markedly different modes of gene expression regulation and their profound effects on gene self-expression regulation.
BRIEFINGS IN BIOINFORMATICS
(2021)
Review
Genetics & Heredity
Sivakumar Vadivel Gnanasundram, Ondrej Bonczek, Lixiao Wang, Sa Chen, Robin Fahraeus
Summary: Continuous genotoxic stress attacks challenge human cells, leading to DNA damage and potentially cancer development. Cells activate the DNA damage response (DDR) to regulate the cell cycle and repair DNA, with the tumor suppressor p53 playing a key role in this process.
Review
Pharmacology & Pharmacy
Malvin L. Pardi, Juanqi Wu, Shunsuke Kawasaki, Hirohide Saito
Summary: This review discusses recent developments of RNA-based synthetic genetic circuits in mammalian cells, including post-transcriptional control methods and auxiliary components, as well as their applications in biomedical and preclinical settings.
ADVANCED DRUG DELIVERY REVIEWS
(2022)
Article
Cell Biology
Ruifan Wu, Shengchun Feng, Fan Li, Gang Shu, Lina Wang, Ping Gao, Xiaotong Zhu, Canjun Zhu, Songbo Wang, Qingyan Jiang
Summary: Obesity is a global health problem associated with metabolic diseases. This study investigates the role of YBX1 in adipogenesis and adipose tissue expansion. The researchers found that YBX1 deficiency inhibited adipocyte differentiation and that YBX1 promotes adipogenesis through ULK1- and ULK2-mediated autophagy. The findings provide insights into the molecular mechanisms and functional importance of YBX1 in regulating autophagy and adipogenesis, highlighting its potential as a therapeutic target for obesity and metabolic diseases.
CELL DEATH & DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Yuting Feng, Yan Zhang, Jie Li, Raha Parvizi Omran, Malcolm Whiteway, Jinrong Feng
Summary: The global transcriptional changes in response to the DNA damage agent MMS in Candida albicans have been explored, with the identification of several genes that are significantly affected. These findings provide insights into the potential roles of genes in DNA repair and antioxidation responses. The study also reveals limited similarity between the transcriptional profile in C. albicans and that in S. cerevisiae in response to MMS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Plant Sciences
Rodrigo S. Reis
Summary: There is a significant gap in our understanding of thermomorphogenesis regulation, specifically in processes involving RNA. This gap presents opportunities for exciting new discoveries in post-transcriptional regulation, while also posing manageable challenges.
JOURNAL OF EXPERIMENTAL BOTANY
(2023)
Article
Biology
Xiaoming Fu, Heta P. Patel, Stefano Coppola, Libin Xu, Zhixing Cao, Tineke L. Lenstra, Ramon Grima, Anna Akhmanova
Summary: This study compares transcriptional parameters with and without correction for cell cycle phases and post-transcriptional noise in yeast cells using smFISH, finding that corrections can significantly reduce errors in parameter estimation. The study also outlines how to adjust for measurement noise in smFISH effectively.
Review
Biochemistry & Molecular Biology
Nikita Shepelev, Olga Dontsova, Maria Rubtsova
Summary: Telomere length is associated with cell proliferative potential and is maintained by telomerase. Telomerase is activated during cellular division and plays a crucial role in processes like regeneration, immune response, embryonic development, and cancer progression. Understanding the regulatory mechanisms of telomerase biogenesis and activity is important for manipulating telomerase and influencing these processes. This review focuses on the molecular mechanisms involved in telomerase regulation and the role of post-transcriptional and post-translational modifications in telomerase biogenesis and function in yeast and vertebrates.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Gabrielle Perron, Pouria Jandaghi, Elham Moslemi, Tamiko Nishimura, Maryam Rajaee, Rached Alkallas, Tianyuan Lu, Yasser Riazalhosseini, Hamed S. Najafabadi
Summary: This study reveals mRNA stability changes accompanying tumor development and progression by decoupling transcriptional and post-transcriptional effects. The findings indicate that mRNA stability changes are 30% less frequent than transcriptional events, and are largely driven by dysregulation of RNA-binding proteins and microRNAs.
COMMUNICATIONS BIOLOGY
(2022)
Review
Oncology
Mouhamed Idrissou, Alexandre Marechal
Summary: mRNA maturation is crucial for proper gene expression, with regulators of this process tightly linked to genome stability. PRP19, an essential E3 ubiquitin ligase, is involved in mRNA splicing, ATR activation, DNA repair, and cell division, highlighting its central role in coordinating mRNA processing and genome protection.
Article
Biochemistry & Molecular Biology
Kendra Reynaud, Anna M. McGeachy, David Noble, Zuriah A. Meacham, Nicholas T. Ingolia
Summary: We conducted an unbiased survey to quantify the regulatory activity of numerous proteins on mRNA translation and decay. Through our analysis of 50,000 protein fragments, we revealed that regulatory activity typically occurs outside RNA-binding domains and aligns with intrinsically disordered regions that can interact with other proteins.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Biology
Yukio Kurihara, Yuko Makita, Masaharu Kawauchi, Ami Kageyama, Tomoko Kuriyama, Minami Matsui
Summary: Recent evidence suggests the existence of readthrough transcripts (RTs), including polycistronic mRNAs, in eukaryotes. This study identifies 271 loci producing polycistronic RTs in Arabidopsis. The accumulation of RTs is increased in NMD-deficient mutants compared to the wild type. Additionally, the translation of the second open reading frames (ORFs) of bicistronic mRNAs is rare. Intergenic splicing (IS) events occur in 158 RTs, and inhibiting splicing promotes the accumulation of RTs.
COMMUNICATIONS BIOLOGY
(2022)
Editorial Material
Cell Biology
Yoseop Yoon, Yongsheng Shi
Summary: In this article, two independent studies successfully reconstituted the processing of human pre-mRNA 3' ends using defined components in vitro. These studies are of great importance for understanding the nature and essential components of this biological process.
GENES & DEVELOPMENT
(2022)
Article
Chemistry, Multidisciplinary
Robin Klimek, Paul G. Donlin-Asp, Claudio Polisseni, Vanessa Hanff, Erin M. Schuman, Alexander Heckel
Summary: A new class of Q-dye molecular beacons can be locally activated with visible light in hippocampal neurons, increasing the monitoring time for neuronal mRNA to 14 hours.
CHEMICAL COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Alison C. Greenlaw, Kris G. Alavattam, Toshio Tsukiyama
Summary: To ensure cell survival during quiescence, cells modulate their gene expression and transcription. By studying the nascent transcriptome, researchers identified over a thousand noncoding RNAs in quiescent and G1 yeast cells, revealing that noncoding transcription plays a larger role in the quiescent state. Furthermore, post-transcriptional regulation is increased in quiescence, affecting both mRNA and ncRNA. The nuclear exosome-NNS pathway was found to regulate the abundance of mRNAs involved in various cellular processes during quiescent entry, highlighting its important biological role in mRNA regulation.
NUCLEIC ACIDS RESEARCH
(2023)
Editorial Material
Oncology
Andrey Kleshnin, Lea Monet, Marina Plays, Hugo Vaysset, Claire Rougeulle, Stephan Vagner
BULLETIN DU CANCER
(2021)
Article
Biochemistry & Molecular Biology
Gaetana Sessa, Belen Gomez-Gonzalez, Sonia Silva, Carmen Perez-Calero, Romane Beaurepere, Sonia Barroso, Sylvain Martineau, Charlotte Martin, Asa Ehlen, Juan S. Martinez, Berangere Lombard, Damarys Loew, Stephan Vagner, Andres Aguilera, Aura Carreira
Summary: BRCA2-deficient cells accumulate DNA-RNA hybrids, and the BRCA2-DDX5 interaction helps in unwinding these structures, enhancing helicase activity and promoting repair of double-strand breaks.
Review
Biochemistry & Molecular Biology
Martin Dutertre, Rym Sfaxi, Stephan Vagner
Summary: The 3'-end processing of pre-mRNAs is globally inhibited by DNA damage in yeast and human cells. There are complex links between pre-mRNA 3'-end processing and the control of genome stability. When DNA damage occurs, genes related to the DNA damage response may escape processing inhibition or be regulated through alternative polyadenylation. Additionally, pre-mRNA 3'-end processing factors play a role in preventing genome instability at sites of DNA damage.
TRENDS IN BIOCHEMICAL SCIENCES
(2021)
Article
Oncology
Isabelle Girault, Julien Adam, Shensi Shen, Severine Roy, Caroline Brard, Sara Faouzi, Emilie Routier, Jeremy Lupu, Sarah Warren, Kristina Sorg, SuFey Ong, Pascale Morel, Jean-Yves Scoazec, Stephan Vagner, Caroline Robert
Summary: The proximity between PD-1 and PD-L1 serves as a new biomarker of anti-PD-1 efficacy in predicting the response of melanoma patients to the treatment, with higher accuracy and predictive ability.
CLINICAL CANCER RESEARCH
(2022)
Article
Genetics & Heredity
Michaela A. Gold, Jenna M. Whalen, Karine Freon, Zixin Hong, Ismail Iraqui, Sarah A. E. Lambert, Catherine H. Freudenreich
Summary: In this study, the fidelity of a restarted fork as it replicates through a CAG/CTG repeat tract was investigated using a yeast model system, revealing that long CAG repeat tracts can lead to increased repeat instability.
Article
Genetics & Heredity
Kamila Schirmeisen, Sarah A. E. Lambert, Karol Kramarz
Summary: DNA lesions can escape their nuclear compartment for repair, while impaired replication forks demonstrate increased mobility and anchor to nuclear pore complexes for specific forms of homologous recombination pathways. Research suggests that SUMO metabolism regulates nuclear positioning, crucial for maintaining genome integrity during replication stress, and is integral to segregating homologous recombination steps during replication fork restart. Routing towards nuclear pore complex anchorage facilitates distinct homologous recombination pathways at stalled replication forks.
Article
Oncology
Biswendu Biswas, Rady Chaaban, Shrena Chakraborty, Alexandre Devaux, Ana Luisa Dian, Anna Minello, Jenny Kaur Singh, Stephan Vagner, Patricia Uguen, Sarah Lambert, Martin Dutertre, Aura Carreira
Summary: This article synthesizes scientific presentations from two international courses held at Institute Curie in 2021, focusing on post-transcriptional gene regulation and genome instability and human disease, bringing together knowledge on RNA metabolism and genome stability maintenance.
BULLETIN DU CANCER
(2022)
Article
Oncology
Biswendu Biswas, Ramdane Guemiri, Mandy Cadix, Celine M. Labbe, Alina Chakraborty, Martin Dutertre, Caroline Robert, Stephan Vagner
Summary: The eIF4A inhibitor silvestrol selectively inhibits the translation of alternatively polyadenylated mRNAs encoding key immune-related proteins, providing a promising approach for anti-cancer therapy targeting the translation initiation complex eIF4F. Through high-throughput analysis, it has been shown that silvestrol differentially inhibits the translation of APA isoforms of various genes in T cells, highlighting the importance of considering mRNA heterogeneity in the understanding of the anti-tumor activities of eIF4A inhibitors.
Article
Biochemistry & Molecular Biology
Alina Chakraborty, Mandy Cadix, Sebastien Relier, Nicolo Taricco, Tina Alaeitabar, Alexandre Devaux, Celine M. Labbe, Sylvain Martineau, Amelie Heneman-Masurel, Pierre Gestraud, Alberto Inga, Nicolas Servant, Stephan Vagner, Martin Dutertre
Summary: This study reveals differential regulation of intronic polyadenylation (IPA) isoform ratio across subcellular compartments during drug response, suggesting distinct patterns of IPA isoform regulation in the transcriptome and translatome, as well as between the nucleus and cytosol.
Article
Biochemistry & Molecular Biology
Rym Sfaxi, Biswendu Biswas, Galina Boldina, Mandy Cadix, Nicolas Servant, Huimin Chen, Daniel R. Larson, Martin Dutertre, Caroline Robert, Stephan Vagner
Summary: The recognition of polyadenylation signals (PAS) in eukaryotic pre-mRNAs is usually coupled to transcription termination, occurring while pre-mRNA is chromatin-bound. However, for some pre-mRNAs, this 3'-end processing occurs post-transcriptionally, i.e., through a co-transcriptional cleavage (CoTC) event downstream of the PAS, leading to chromatin release and subsequent PAS cleavage in the nucleoplasm. These findings indicate that CoTC-type cleavage of pre-mRNAs, followed by PAS cleavage in the nucleoplasm, allows certain pre-mRNAs to escape 3'-end processing inhibition in response to UV-induced DNA damage.
Article
Genetics & Heredity
Manuel Lera-Ramirez, Jurg Bahler, Juan Mata, Kim Rutherford, Charles S. Hoffman, Sarah Lambert, Snezhana Oliferenko, Sophie G. Martin, Kathleen L. Gould, Li-Lin Du, Sarah A. Sabatinos, Susan L. Forsburg, Olaf Nielsen, Paul Nurse, Valerie Wood
Summary: Standardized nomenclature for genes, gene products, and isoforms is crucial for clear communication and efficient sharing of scientific data. This publication extends the fission yeast clade gene nomenclature guidelines to support curation efforts at PomBase, introducing guidelines for noncoding RNA genes and updating allele and genotype nomenclature. Adoption of these rules will improve consistency in gene and genotype nomenclature and enhance machine-readability in publications or datasets.
Article
Cell Biology
Melissa Leriche, Clara Bonnet, Jagannath Jana, Gita Chhetri, Sabrina Mennour, Sylvain Martineau, Vincent Pennaneach, Didier Busso, Xavier Veaute, Pascale Bertrand, Sarah Lambert, Kumar Somyajit, Patricia Uguen, Stephan Vagner
Summary: RNA-binding protein 53BP1 is found to directly interact with Okazaki fragments and its recruitment is affected by RNA enzyme processing. RNA primers contribute to the recruitment of 53BP1 at replication forks, and depletion of 53BP1 leads to the accumulation of S-phase poly(ADP-ribose).
Article
Biochemical Research Methods
Shensi Shen, Isabelle Girault, Helene Malka-Mahieu, Caroline Robert, Stephan Vagner
Summary: This protocol describes a procedure utilizing proximity ligation assay for direct visualization and absolute quantification of the eIF4F complex per cell, allowing for detailed analysis of its subcellular localization.