Article
Cell Biology
Juanjuan Xie, Domenico Libri, Odil Porrua
Summary: Transcription termination is an essential step in the transcription process, allowing the release of transcripts and recycling of the polymerase. It is crucial for preventing interference between neighboring transcription units and conflicts with other DNA-associated processes. This review discusses the mechanisms of transcription termination by different classes of eukaryotic RNAPs and highlights interesting commonalities.
JOURNAL OF CELL SCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Vytaute Boreikaite, Lori A. Passmore
Summary: The formation of the 3' end of a eukaryotic mRNA is a crucial step in mRNA maturation. Protein factors such as CPSF and CPF are responsible for cleaving the pre-mRNA, adding a poly(A) tail, and regulating transcription. The selection of the cleavage site and the length of the poly(A) tail play important roles in mRNA translation, stability, and localization.
ANNUAL REVIEW OF BIOCHEMISTRY
(2023)
Article
Cell Biology
Ananthanarayanan Kumar, Conny W. H. Yu, Juan B. Rodriguez-Molina, Xiao-Han Li, Stefan M. V. Freund, Lori A. Passmore
Summary: The translation provided describes a detailed study of the essential subunit Fip1 in the CPF/CPSF multiprotein complex, revealing the importance of its dynamics in coordinating cleavage and polyadenylation processes at the 3' end.
GENES & DEVELOPMENT
(2021)
Article
Biochemistry & Molecular Biology
Ahmet C. Berkyurek, Giulia Furlan, Lisa Lampersberger, Toni Beltran, Eva-Maria Weick, Emily Nischwitz, Isabela Cunha Navarro, Fabian Braukmann, Alper Akay, Jonathan Price, Falk Butter, Peter Sarkies, Eric A. Miska
Summary: PIWI-interacting RNAs (piRNAs) are small RNAs that regulate germ cell development in animals, and in the nematode Caenorhabditis elegans, the core subunit RPB-9 of RNA polymerase II (RNA Pol II) is identified as essential for piRNA-mediated gene silencing. RPB-9 is required for piRNA biogenesis by recruiting the Integrator complex at piRNA genes for transcriptional termination, suggesting the piRNA pathway has evolved to utilize a mechanism originally used for transcription fidelity.
Article
Biochemistry & Molecular Biology
Fiorella Scagnoli, Alessandro Palma, Annarita Favia, Claudio Scuoppo, Barbara Illi, Sergio Nasi
Summary: Deregulation of the MYC oncoprotein is a common event in cancer, and inhibiting its activity can restrain tumor development. This study shows that MYC regulates transcription termination by affecting a methylated target, R1810me2s, and Omomyc can counteract this effect. Omomyc also affects RNAPII elongation and reshapes gene expression, suggesting an MYC/PRMT5/RNAPII axis that contributes to altered gene expression in cancer.
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)
Review
Biochemistry & Molecular Biology
Araceli Gonzalez-Jimenez, Adrian Campos, Francisco Navarro, Andres Clemente-Blanco, Olga Calvo
Summary: Phosphorylation can regulate the function of RNA polymerases and affect the coordination with other nuclear processes. Apart from Rpb1-CTD, other RNAPII subunits are phosphorylated, but little is known about phosphorylation of RNAPI and RNAPIII. Different subunits of RNAPI and RNAPIII may be susceptible to phosphorylation, indicating a potential coordination mechanism among the three RNAPs.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Cell Biology
Moritz Schmidt, Florian Kluge, Felix Sandmeir, Uwe Kuehn, Peter Schaefer, Christian Tueting, Christian Ihling, Elena Conti, Elmar Wahle
Summary: In this study, the endonucleolytic cleavage of eukaryotic mRNA 3' ends followed by polyadenylation was reconstituted using overproduced and purified proteins. A minimal list of 14 essential polypeptides and 2 stimulatory polypeptides for RNA processing were identified. Key findings include the stimulation of cleavage by cleavage factor I and the essential requirement of RBBP6 in contacting and activating the endonuclease CPSF73.
GENES & DEVELOPMENT
(2022)
Review
Immunology
Aarthi Vijayakumar, Annsea Park, Joan A. Steitz
Summary: Eukaryotic mRNA 3'-end processing is a critical step in gene expression regulation, and disruption of this process by viral proteins can lead to host shutoff and impaired antiviral response. Viruses may utilize the effects of read-through transcripts to modulate host protein production and cellular machinery.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Donghui Choe, Kangsan Kim, Minjeong Kang, Seung-Goo Lee, Suhyung Cho, Bernhard Palsson, Byung-Kwan Cho
Summary: The study used Term-Seq technology to analyze the 3 '-end of transcripts in Escherichia coli, revealing multiple classes of 3 '-termini and designing novel synthetic metabolic valves for metabolic flux regulation, laying a foundation for 3 '-UTR engineering in synthetic biology applications.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biology
Natalia Petrenko, Kevin Struhl
Summary: Differences in the transcriptional initiation process exist among eukaryotic species, such as the dynamic bridge of Mediator and variations in TBP occupancy. TFIID interacts strongly at downstream regions of the initiation site in flies, contrasting with yeast and mammals. The Mediator subunit Med26 and Taf7 interact near the Pol II pause region, but only in subsets of genes.
Article
Multidisciplinary Sciences
Hidefumi Suzuki, Ryota Abe, Miho Shimada, Tomonori Hirose, Hiroko Hirose, Keisuke Noguchi, Yoko Ike, Nanami Yasui, Kazuki Furugori, Yuki Yamaguchi, Atsushi Toyoda, Yutaka Suzuki, Tatsuro Yamamoto, Noriko Saitoh, Shigeo Sato, Chieri Tomomori-Sato, Ronald C. Conaway, Joan W. Conaway, Hidehisa Takahashi
Summary: This study demonstrates the importance of Mediator in the transcription termination of replication-dependent histone genes. Mediator plays a role in pausing RNA polymerase II at the transcript end sites of these genes by associating with Cajal bodies, thereby facilitating the subsequent 3'-end processing.
NATURE COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Chaima Azouzi, Mariam Jaafar, Christophe Dez, Raghida Abou Merhi, Annick Lesne, Anthony K. Henras, Olivier Gadal
Summary: The study highlights the coupling between rRNA production and nascent rRNA folding, showing that RNA folding acts as an anti-pausing mechanism and favors transcription elongation. Defects in co-transcriptional folding of rRNA may induce Pol I pausing, and premature termination of transcription can potentially control rRNA production in vivo.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Multidisciplinary Sciences
Buki Kwon, Mervin M. Fansler, Neil D. Patel, Jihye Lee, Weirui Ma, Christine Mayr
Summary: Multi-UTR genes express their alternative 3' UTR isoforms in a cell type-specific manner. Transcriptional enhancers, along with transcription factors, regulate the expression of these isoforms by influencing the cleavage activity of polyadenylation sites.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Craig J. Marshall, M. Zuhaib Qayyum, Julie E. Walker, Katsuhiko S. Murakami, Thomas J. Santangelo
Summary: Transcription termination is an important process in regulating gene expression, and the protein Eta has been identified as one of the factors involved in disrupting transcription elongation complexes. By studying the biochemical activities and crystal structure of Eta, researchers have gained insight into its role in transcription termination. The susceptibility of transcription elongation complexes to disruption by termination factors highlights the common features of transcription termination mechanisms.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Takayuki Nojima, Tomas Gomes, Ana Rita Fialho Grosso, Hiroshi Kimura, Michael J. Dye, Somdutta Dhir, Maria Carmo-Fonseca, Nicholas J. Proudfoot
Article
Cell Biology
Pawel Grzechnik, Michal Ryszard Gdula, Nick J. Proudfoot
GENES & DEVELOPMENT
(2015)
Article
Biochemistry & Molecular Biology
Elodie Hatchi, Konstantina Skourti-Stathaki, Steffen Ventz, Luca Pinello, Angela Yen, Kinga Kamieniarz-Gdula, Stoil Dimitrov, Shailja Pathania, Kristine M. McKinney, Matthew L. Eaton, Manolis Kellis, Sarah J. Hill, Giovanni Parmigiani, Nicholas J. Proudfoot, David M. Livingston
Article
Biochemistry & Molecular Biology
Ashish Dhir, Somdutta Dhir, Nick J. Proudfoot, Catherine L. Jopling
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2015)
Article
Biochemistry & Molecular Biology
Ashish Dhir, Somdutta Dhir, Nick J. Proudfoot, Catherine L. Jopling
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2015)
Article
Biology
Ilaria Pettinati, Pawel Grzechnik, Claudia Ribeiro de Almeida, Jurgen Brem, Michael A. McDonough, Somdutta Dhir, Nick J. Proudfoot, Christopher J. Schofield
Article
Biochemistry & Molecular Biology
Kinga Kamieniarz-Gdula, Michal R. Gdula, Karin Panser, Takayuki Nojima, Joan Monks, Jacek R. Wisniewski, Joey Riepsaame, Neil Brockdorff, Andrea Pauli, Nick J. Proudfoot
Article
Biochemistry & Molecular Biology
Lea H. Gregersen, Richard Mitter, Alejandro P. Ugalde, Takayuki Nojima, Nicholas J. Proudfoot, Reuven Agami, Aengus Stewart, Jesper Q. Svejstrup
Review
Genetics & Heredity
Kinga Kamieniarz-Gdula, Nick J. Proudfoot
TRENDS IN GENETICS
(2019)
Article
Biochemistry & Molecular Biology
Sue Mei Tan-Wong, Somdutta Dhir, Nick J. Proudfoot
Article
Multidisciplinary Sciences
Esther Griesbach, Margarita Schlackow, William F. Marzluff, Nick J. Proudfoot
Summary: The gene encoding H2A.X histone variant produces two different mRNA isoforms, which have differential effects on DNA damage repair depending on the cell types.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Martin S. C. Larke, Ron Schwessinger, Takayuki Nojima, Jelena Telenius, Robert A. Beagrie, Damien J. Downes, A. Marieke Oudelaar, Julia Truch, Bryony Graham, M. A. Bender, Nicholas J. Proudfoot, Douglas R. Higgs, Jim R. Hughes
Summary: Gene transcription is regulated mainly at the level of initiation, with enhancers playing a key role in this process. By evaluating promoter-proximal transcription in the context of differential gene expression, it was shown that changes in transcription initiation, rather than release of Pol II pausing, predominantly control gene expression during differentiation. Using genetically engineered mouse models, it was confirmed that enhancers regulate Pol II recruitment and/or initiation to modulate gene expression.
Review
Cell Biology
Takayuki Nojima, Nick J. Proudfoot
Summary: Mammalian genomes express protein-coding and non-coding RNA genes. Recent studies have revealed differences in transcription initiation and termination between non-coding RNA genes and protein-coding genes, which are relevant to genomic stress and DNA damage.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2022)
Correction
Cell Biology
Takayuki Nojima, Nick J. Proudfoot
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Inna Zukher, Gwendal Dujardin, Rui Sousa-Luis, Nick J. Proudfoot
Summary: This study demonstrates the role of non-cleaving Cas9 (dCas9) in transcriptional regulation, showing its ability to precisely control RNA polymerase II transcriptional pausing and termination, with minimal effects on alternative splicing.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
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)