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)
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
Yajing Hao, Ting Cai, Chang Liu, Xuan Zhang, Xiang-Dong Fu
Summary: In eukaryotic cells, the coupled reaction for cleavage and polyadenylation (CPA) at the 3' end of transcripts is a key step in generating mature mRNA. Alternative polyadenylation (APA) can produce mRNA isoforms with different 3' ends, which may affect the coding sequence or 3' UTR length. Recent studies have shown that APA can occur after transcription through a mechanism called sequential APA. This mini-review focuses on these new mechanisms of post-transcriptional APA.
MOLECULES AND CELLS
(2023)
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
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
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)
Review
Virology
Marilyn Whelan, Martin Pelchat
Summary: The promoter-proximal pause induced by the binding of DSIF and NELF to RNAP II is a crucial step in the regulation of metazoan gene expression. It plays important roles in maintaining chromatin landscape and facilitating quick transcriptional response to stimuli. Additionally, it is involved in the life cycle of RNA viruses such as HIV, IAV, and HDV.
Article
Biochemistry & Molecular Biology
Miguel Montez, Maria Majchrowska, Michal Krzyszton, Grzegorz Bokota, Sebastian Sacharowski, Magdalena Wrona, Ruslan Yatusevich, Ferran Massana, Dariusz Plewczynski, Szymon Swiezewski
Summary: We investigated noncoding RNA transcription upstream of the Arabidopsis DOG1 gene and found a positive role of co-directional transcription in regulating the expression of the downstream gene. The transcription activity on the promoter of DOG1 gene produced various lncRNAs named PUPPIES, which responded to salt stress and enhanced DOG1 expression. This resulted in delayed seed germination. The positive role of pervasive PUPPIES transcription was associated with pausing of RNA polymerase II, slower transcription, and higher transcriptional burst size.
Article
Biochemical Research Methods
Xiaohui Wu, Tao Liu, Congting Ye, Wenbin Ye, Guoli Ji
Summary: APA plays a crucial role in transcriptome diversity and gene expression regulation. The newly developed tool scAPAtrap can accurately identify poly(A) sites at the whole genome level in individual cells, even for sites with low read coverage, without relying on priori genome annotation. Compared to existing methods, scAPAtrap shows higher accuracy and sensitivity in identifying poly(A) sites, making it a valuable tool for exploring APA dynamics and heterogeneous APA isoform expression at the single-cell level.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Multidisciplinary Sciences
Chirangini Pukhrambam, Vadim Molodtsov, Mahdi Kooshkbaghi, Ammar Tareen, Hoa Vu, Kyle S. Skalenko, Min Su, Zhou Yin, Jared T. Winkelman, Justin B. Kinney, Richard H. Ebright, Bryce E. Nickels
Summary: In sigma-dependent transcriptional pausing, the presence or absence of GreB determines whether the paused state involves backtracking or scrunched by 2-4 base pairs or 2-3 base pairs respectively. The consensus sequence T(-3)N(-2)Y(-1)G(+1) is associated with pausing in both initial transcription and transcription elongation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Lorenzo Gallicchio, Gonzalo H. Olivares, Cameron W. Berry, Margaret T. Fuller
Summary: Alternative cleavage and polyadenylation (APA) is a co-transcriptional RNA processing process that greatly affects gene expression. APA occurs naturally during development and cellular differentiation, and changes in APA are associated with pathological states. The understanding of APA regulation and its impact on gene expression is still incomplete.
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
Biochemistry & Molecular Biology
Michael Tellier, Justyna Zaborowska, Jonathan Neve, Takayuki Nojima, Svenja Hester, Marjorie Fournier, Andre Furger, Shona Murphy
Summary: CDK9 is a critical kinase for the productive transcription of protein-coding genes. Loss of CDK9 activity not only leads to premature termination and loss of polyadenylation of transcripts, but also causes the loss of factors involved in coupling transcription elongation and termination. These findings highlight the important roles of CDK9 in transcription process.
Article
Multidisciplinary Sciences
Rishi K. Vishwakarma, M. Zuhaib Qayyum, Paul Babitzke, Katsuhiko S. Murakami
Summary: NusG is a transcription elongation factor that induces transcription pausing in bacteria by interacting with a specific sequence in the non-template DNA strand. The interaction between NusG and the DNA rearranges the transcription bubble and affects the conformational changes of RNA polymerase, leading to the inhibition of RNA synthesis. This mechanism of pausing is widely conserved in bacteria.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Vivekanandan Ramalingam, Xinyang Yu, Brian D. Slaughter, Jay R. Unruh, Kaelan J. Brennan, Anastasiia Onyshchenko, Jeffrey J. Lange, Malini Natarajan, Michael Buck, Julia Zeitlinger
Summary: Lola-I, a Drosophila zinc finger transcription factor, can regulate the promoter state independently of gene activation. It makes the target promoters accessible and acquire paused RNA polymerase II throughout the embryo. This promoter transition is crucial for tissue-specific target gene activation. Lola-I mediates this function by depleting promoter nucleosomes.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Nova Fong, Tassa Saldi, Ryan M. Sheridan, Michael A. Cortazar, David L. Bentley
Article
Cell Biology
Christopher C. Ebmeier, Benjamin Erickson, Benjamin L. Allen, Mary A. Allen, Hyunmin Kim, Nova Fong, Jeremy R. Jacobsen, Kaiwei Liang, Ali Shilatifard, Robin D. Dowell, William M. Old, David L. Bentley, Dylan J. Taatjes
Article
Cell & Tissue Engineering
Shanshan Pei, Mohammad Minhajuddin, Biniam Adane, Nabilah Khan, Brett M. Stevens, Stephen C. Mack, Sisi Lai, Jeremy N. Rich, Anagha Inguva, Kevin M. Shannon, Hyunmin Kim, Aik-Choon Tan, Jason R. Myers, John M. Ashton, Tobias Neff, Daniel A. Pollyea, Clayton A. Smith, Craig T. Jordan
Article
Computer Science, Interdisciplinary Applications
Minjae Yoo, Jimin Shin, Hyunmin Kim, Jihye Kim, Jaewoo Kang, Aik Choon Tan
COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE
(2019)
Article
Cell Biology
Tassa Saldi, Nova Fong, David L. Bentley
GENES & DEVELOPMENT
(2018)
Article
Biochemistry & Molecular Biology
Erica L. Clinkenbeard, Courtney Turpin, Jieyun Jiang, Martha L. Peterson, Brett T. Spear
Article
Biochemistry & Molecular Biology
Tomomi M. Yamamoto, Alexandra McMellen, Zachary L. Watson, Jennifer Aguilera, Rebecca Ferguson, Elmar Nurmemmedov, Tanay Thakar, George-Lucian Moldovan, Hyunmin Kim, Diana M. Cittelly, Annette M. Joglar, Elyse P. Brennecke, Heidi Wilson, Kian Behbakht, Matthew J. Sikora, Benjamin G. Bitler
MOLECULAR CARCINOGENESIS
(2019)
Article
Oncology
Zachary L. Watson, Tomomi M. Yamamoto, Alexandra McMellen, Hyunmin Kim, Connor J. Hughes, Lindsay J. Wheeler, Miriam D. Post, Kian Behbakht, Benjamin G. Bitler
CLINICAL EPIGENETICS
(2019)
Article
Evolutionary Biology
Alexandra N. Nail, Jeramiah J. Smith, Martha L. Peterson, Brett T. Spear
GENOME BIOLOGY AND EVOLUTION
(2020)
Article
Oncology
Reema S. Wahdan-Alaswad, Susan M. Edgerton, Hiba Salem, Hyun Min Kim, Aik Choon Tan, Jessica Finlay-Schultz, Elizabeth A. Wellberg, Carol A. Sartorius, Britta M. Jacobsen, Bryan R. Haugen, Bolin Liu, Ann D. Thor
Summary: The study revealed clinically significant adverse interactions between THRT, estrogenic, and oncogenic signaling in patients with steroid receptor-positive, lymph node-negative breast cancer.
CLINICAL CANCER RESEARCH
(2021)
Article
Genetics & Heredity
Alexandra N. Nail, Brett T. Spear, Martha L. Peterson
Summary: The mammalian Cytochrome P450 (Cyp) gene superfamily encodes enzymes involved in metabolic pathways and are frequently expressed in the liver. Despite high sequence similarity, Cyp2a4 and Cyp2a5 genes exhibit differential expression in adult mouse liver, potentially regulated by unique antisense long noncoding RNAs. These antisense transcripts, found in different liver zones, show sex-biased expression patterns earlier than their corresponding sense mRNAs, providing insights into transcriptional and post-transcriptional mechanisms governing Cyp2a4 and Cyp2a5 expression.
Article
Gastroenterology & Hepatology
Jieyun Jiang, Courtney Turpin, Guofang (Shirley) Qiu, Mei Xu, Eun Lee, Terry D. Hinds, Martha L. Peterson, Brett T. Spear
Summary: Zhx2 acts as an oncogene in DEN-induced HCC model, and its expression is associated with clinical pathological parameters in patients with HCC.
HEPATOLOGY COMMUNICATIONS
(2022)
Article
Oncology
Ayman Oweida, Mohammad K. Hararah, Andy Phan, David Binder, Shilpa Bhatia, Shelby Lennon, Sanjana Bukkapatnam, Benjamin Van Court, Nomin Uyanga, Laurel Darragh, Hyun Min Kim, David Raben, Aik Choon Tan, Lynn Heasley, Eric Clambey, Raphael Nemenoff, Sana D. Karam
CLINICAL CANCER RESEARCH
(2018)
Article
Oncology
Jessica Finlay-Schultz, Austin E. Gillen, Heather M. Brechbuhl, Joshua J. Ivie, Shawna B. Matthews, Britta M. Jacobsen, David L. Bentley, Peter Kabos, Carol A. Sartorius