Review
Cell Biology
Lorenzo Pavanello, Michael Hall, Gerlof Sebastiaan Winkler
Summary: Accurate and precise regulation of gene expression in eukaryotes involves the coordinated control of transcription, mRNA stability, and translation. Recent progress has been made in understanding the role of sequence elements in the 3' untranslated region in mRNA degradation regulation. The recruitment of the Ccr4-Not complex to target mRNA is a critical step in mRNA decay regulation. This article reviews the role of the human Ccr4-Not complex in cytoplasmic deadenylation of mRNA, focusing on its recruitment mechanisms and general mechanisms involving the poly(A) tail.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Noriyuki Azuma, Tadashi Yokoi, Taku Tanaka, Emiko Matsuzaka, Yuki Saida, Sachiko Nishina, Miho Terao, Shuji Takada, Maki Fukami, Kohji Okamura, Kayoko Maehara, Tokiwa Yamasaki, Jun Hirayama, Hiroshi Nishina, Hiroshi Handa, Yuki Yamaguchi
Summary: This study reports the molecular and genetic characterization of Integrator complex subunit 15 (INTS15). INTS15 is highly expressed in the eye and brain, and it interacts with the Integrator complex to support small nuclear RNA 3' end processing. Knockdown of INTS15 leads to missplicing of numerous genes and affects genes associated with eye and brain development.
HUMAN MOLECULAR GENETICS
(2023)
Article
Multidisciplinary Sciences
Yan Xu, Zhuowei Zhou, Xinmei Kang, Lijie Pan, Chang Liu, Xiaoqi Liang, Jiajie Chu, Shuai Dong, Yanli Li, Qiuli Liu, Yuetong Sun, Shanshan Yu, Qi Zhang
Summary: This study reveals the important role of Mettl3-mediated RNA m(6)A modification in postnatal liver development, specifically through regulation of the Hnf4a-centered transcriptional network.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Christopher Duncan-Lewis, Ella Hartenian, Valeria King, Britt A. Glaunsinger
Summary: RNA abundance is sensitive to perturbations in decay and synthesis rates, with RNA polymerase II transcription and cytoplasmic mRNA degradation influencing each other. Widespread mRNA decay during early apoptosis represses RNAPII transcription through a feedback mechanism that requires active cytoplasmic mRNA degradation. This gene regulatory mechanism, involving the connection between mRNA decay and transcription, is conserved and important for cellular responses to threats.
Article
Multidisciplinary Sciences
Philippe J. Batut, Xin Yang Bing, Zachary Sisco, Joao Raimundo, Michal Levo, Michael S. Levine
Summary: Past studies have provided contradictory claims about the role of genome organization in gene activity regulation. This study demonstrates that the Drosophila genome is organized by two independent classes of regulatory sequences, tethering elements and insulators. These two levels of genome organization operate independently to ensure precise transcriptional dynamics and reliable complex patterning processes.
Article
Multidisciplinary Sciences
Chunxia Zhang, Meng Wang, Yisi Li, Yi Zhang
Summary: Transcriptional regulation is important in early mouse embryo development. Using a new technique, the mRNA translation landscape of mouse preimplantation embryos was revealed, showing the critical role of active translation of maternal mRNAs in maternal-to-zygotic transition. The study also identified two maternal factors required for chromatin reprogramming and zygotic genome activation.
Article
Multidisciplinary Sciences
Iva Salamon, Yongkyu Park, Terezija Miskic, Janja Kopic, Paul Matteson, Nicholas F. Page, Alfonso Roque, Geoffrey W. McAuliffe, John Favate, Marta Garcia-Forn, Premal Shah, Milos Judas, James H. Millonig, Ivica Kostovic, Silvia De Rubeis, Ronald P. Hart, Zeljka Krsnik, Mladen-Roko Rasin
Summary: This study reveals the critical role of RNA-binding protein CELF4 in prenatal neocortical development, specifically in the translation of synaptic mRNA and the development of subplate synapses. The study also highlights the enrichment of autism spectrum disorder risk genes in subplate neurons.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Haobin Jiang, Lina Bai, Shen Song, Qianqian Yin, Anteng Shi, Bin Zhou, Hong Lian, Houzao Chen, Cheng-Ran Xu, Yanchun Wang, Yu Nie, Shengshou Hu
Summary: In this study, the role of EZH2 in epicardial development was investigated. The results demonstrate that EZH2 promotes epicardial cell migration by suppressing TIMP3 transcription, which is vital for heart development. Moreover, epicardial Ezh2 deficiency-induced TIMP3 upregulation leads to extracellular matrix reconstruction in the embryonic myocardium.
LIFE SCIENCE ALLIANCE
(2023)
Article
Chemistry, Multidisciplinary
Michael J. Mitchell, Kelsey L. Swingle, Hannah C. Safford, Hannah C. Geisler, Alex G. Hamilton, Ajay S. Thatte, Margaret M. Billingsley, Ryann A. Joseph, Kaitlin Mrksich, Marshall S. Padilla, Aditi A. Ghalsasi, Mohamad-Gabriel Alameh, Drew Weissman
Summary: This study developed ionizable lipid nanoparticles (LNPs) for mRNA delivery to the placenta to regulate placental vasodilation. By designing a combination of ionizable lipids, a lead LNP was identified that can deliver mRNA to trophoblasts, endothelial cells, and immune cells in the placenta. Injection of LNPs encapsulated with VEGF-A mRNA resulted in placental vasodilation, demonstrating the potential of mRNA LNPs for protein replacement therapy to treat placental disorders during pregnancy.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Matthew P. Swaffer, Georgi K. Marinov, Huan Zheng, Lucas Fuentes Valenzuela, Crystal Yee Tsui, Andrew W. Jones, Jessica Greenwood, Anshul Kundaje, William J. Greenleaf, Rodrigo Reyes-Lamothe, Jan M. Skotheim
Summary: A fundamental feature of cellular growth is that protein and RNA amounts increase with cell size to maintain constant concentrations. In budding yeast, RNA polymerase II (RNAPII) is identified as the limiting factor scaling mRNA transcription with cell size. The global RNAPII transcription is determined by the mass action recruitment kinetics of unengaged nucle-oplasmic RNAPII to the genome. However, this increase in transcription with size is partially compensated for by a decrease in mRNA decay rates as cells enlarge.
Article
Biochemistry & Molecular Biology
Joshua C. Bufton, Kyle T. Powers, Jenn-Yeu A. Szeto, Christine Toelzer, Imre Berger, Christiane Schaffitzel
Summary: UPF3 is a key factor in nonsense-mediated mRNA decay (NMD) that regulates mRNA surveillance and gene expression. UPF3A and UPF3B share structural and functional similarities with paraspeckle proteins, binding RNA and UPF2 through specific domains. Disease-causing mutation Y160D in UPF3B disrupts the binding to UPF2, while UPF3A, upregulated in patients with the mutation, shows higher affinity for UPF2. The characterization of UPF3's middle-domain reveals its essential role in NMD.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Pragyan Singh, Anusha Chaudhuri, Mayukh Banerjea, Neeraja Marathe, Biswadip Das
Summary: The Nrd1p-Nab3p-Sen1p (NNS) complex plays a universal role in nuclear decay of all categories of aberrant mRNAs in yeast, with the interaction domain of Nrd1p and RNA Pol II being crucial for its function.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
Belen Pacheco-Fiallos, Matthias K. Vorlaender, Daria Riabov-Bassat, Laura Fin, Francis J. O'Reilly, Farja I. Ayala, Ulla Schellhaas, Juri Rappsilber, Clemens Plaschka
Summary: Newly made mRNAs are recognized and organized by the essential TREX complex for nuclear export. Cryo-electron microscopy and tomography structures reveal that mRNAs are recognized through multivalent interactions between TREX subunit ALYREF and mRNP-bound exon junction complexes. Endogenous mRNPs form compact globules that are coated by multiple TREX complexes, providing a framework to understand mRNA biogenesis and export.
Article
Medicine, Research & Experimental
Dandan Song, Xiaosheng Wang
Summary: The study proposes a new mRNA-based ITH evaluation algorithm called DEPTH2, which effectively evaluates the levels of intratumor heterogeneity and is associated with various cancer characteristics such as tumor progression and genomic instability.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Agriculture, Dairy & Animal Science
Pengna Luo, Ziyang Wang, Chuanchen Su, Huihong Li, Huaiyong Zhang, Yanqun Huang, Wen Chen
Summary: This study obtained chicken GLUT4 mRNA sequences and conducted bioinformatics analysis on its genomic structure, splicing pattern, subcellular localization prediction and homologous comparisons. RT-qPCR detection showed that chicken GLUT4 is distributed in bird's liver and striated muscles, and at least 14 transcripts encoding 12 types of amino acid sequences were produced through alternative splicing and polyadenylation. These isoforms may play overlapping and distinct roles in chicken during development.