Article
Genetics & Heredity
Yixi Sun, Yangwen Qian, Hai-Xi Sun, Min Chen, Yuqin Luo, Xiaojing Xu, Kai Yan, Liya Wang, Junjie Hu, Minyue Dong
Summary: In females with DDX3X-related intellectual disability, extreme skewing of XCI in the mutant allele was found, which was insufficient to reverse the phenotype of neurodevelopmental disorders related to DDX3X defects.
FRONTIERS IN GENETICS
(2022)
Article
Multidisciplinary Sciences
Agata Izabela Kalita, Eric Marois, Magdalena Kozielska, Franz J. Weissing, Etienne Jaouen, Martin M. Moeckel, Frank Ruehle, Falk Butter, M. Felicia Basilicata, Claudia Isabelle Keller Valsecchi
Summary: The discovery of the sex chromosome activation (SOA) gene as a master regulator of dosage compensation (DC) in Anopheles mosquitoes sheds light on the evolutionary steps leading to the establishment of a chromosome-specific fine-tuning mechanism. The male isoform of the SOA gene encodes a DNA-binding protein that binds the promoters of active X chromosomal genes and expressing it induces DC in female cells. Male mosquitoes lacking SOA or female mosquitoes expressing the male isoform exhibit X chromosome misregulation and developmental delay.
Article
Plant Sciences
Tania Chakraborty, Joshua T. Trujillo, Timmy Kendall, Rebecca A. Mosher
Summary: In this study, the researchers identified the second subunit of Pol IV, NRPD2, in grass plants and found that it functions with NRPD1 in small RNA production and CHH methylation in leaves. The homozygous nrpd2 mutants do not have gametophytic defects or embryo lethality, but adult plants are dwarf and sterile.
Article
Multidisciplinary Sciences
Linyu Zuo, Guanwei Zhang, Matthew Massett, Jun Cheng, Zicong Guo, Liang Wang, Yifei Gao, Ru Li, Xu Huang, Pilong Li, Zhi Qi
Summary: FUS/EWS/TAF15 (FET) fusion oncoproteins, containing low complexity domain, form biomolecular condensates that recruit RNA polymerase II, promoting gene transcription. Through the development of a single-molecule assay, a causal relationship between the formation of condensates on DNA and gene transcription is supported, along with the identification of a threshold number of fusion-binding DNA elements required for the formation of FET protein condensates.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Trevor van Eeuwen, Tao Li, Hee Jong Kim, Jose J. Gorbea Colon, Mitchell Parker, Roland L. Dunbrack, Benjamin A. Garcia, Kuang-Lei Tsai, Kenji Murakami
Summary: During transcription initiation, TFIIH marks RNA polymerase II by phosphorylating Ser5 of Rpb1's CTD, followed by modifications related to transcription elongation, mRNA processing, and histone dynamics. The structure of TFIIK helps extend the proposed model of the CTD path to TFIIH's active site.
Article
Biology
Shu-Hao Liou, Sameer K. Singh, Robert H. Singer, Robert A. Coleman, Wei-Li Liu
Summary: Liou et al. report a 4.6 angstrom resolution structure of the human p53/RNA polymerase II assembly, using single particle cryoelectron microscopy. This study suggests that p53's functional domains regulate the DNA binding activity of RNA polymerase II, providing insights into p53-regulated gene expression.
COMMUNICATIONS BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Sylvain Egloff
Summary: CDK9 plays a crucial role in releasing paused RNAPII for productive elongation, thereby facilitating efficient mRNA synthesis. Its involvement in coordinating elongation with transcription initiation and termination highlights its significance, with aberrant CDK9 activity linked to various human pathologies.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Multidisciplinary Sciences
Kim Nguyen, Turnee N. Malik, John C. Chaput
Summary: The primary obstacle of using DNA enzymes as gene silencing agents in clinical applications is their low activity. This study demonstrates the chemical evolution of a modified DNAzyme with strong catalytic activity under near physiological conditions. The modified enzyme achieves similar turnover rates as the unmodified parent sequence under forcing conditions. The results of this study illustrate the potential of chemical evolution in discovering new chemotype combinations for therapeutic applications of DNAzymes.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Anna Sawicka, Gabriel Villamil, Michael Lidschreiber, Xavier Darzacq, Claire Dugast-Darzacq, Bjoern Schwalb, Patrick Cramer
Summary: In human cells, shortening CTD by half does not affect pre-mRNA synthesis and processing, but it does impact Pol II pausing, enhancer element transcription, and transcription activation after MAP kinase pathway stimulation. This suggests that a long CTD is necessary for efficient recruitment of Pol II to target genes for rapid activation.
Article
Multidisciplinary Sciences
Sandra Schilbach, Haibo Wang, Christian Dienemann, Patrick Cramer
Summary: This study presents an atomic model for the yeast preinitiation complex (PIC) with core mediator, revealing the molecular details of RNA polymerase II (Pol II) transcription initiation. The structure of the mediator middle module was optimized, and the missing subunit Med1 was identified. The study found that the flexible C-terminal repeat domain (CTD) of Pol II forms defined interactions with the mediator head and middle modules, as well as other regions of the mediator. The binding mode between the yeast mediator and Pol II differs from the human counterpart.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biology
Shao-Pei Chou, Adriana K. Alexander, Edward J. Rice, Lauren A. Choate, Charles G. Danko
Summary: This study investigates how DNA sequence differences affect the dynamics and position of RNA polymerase II (Pol II) during transcription. The researchers found that DNA sequence motifs are key determinants of Pol II initiation and pause positions, and that initiation site selection follows a stochastic process similar to Brownian motion. Additionally, they discovered that differences in transcription termination impact the structure and stability of mature mRNA, and that allelic changes in transcription affect mRNA and ncRNA expression across genomic domains.
Article
Medicine, Research & Experimental
Hyun-Soo Kim, Yoon Jeon, Yoon Ok Jang, Ho Lee, Yong Shin, Chang-Woo Lee
Summary: This study reveals that mammalian Ssu72 plays a crucial role in the transcriptional regulation of various genes through transcriptional elongation rather than polyadenylation or RNA processing. Depletion of Ssu72 leads to Pol II pausing and elongation defects, and reduced transcriptional elongation efficiency primarily affects the expression levels of actively transcribed genes.
Article
Biochemistry & Molecular Biology
Shuo Cao, Haoran Zhu, Jinru Cui, Sun Liu, Yuhe Li, Junfang Shi, Junyuan Mo, Zihan Wang, Hailan Wang, Jiaxin Hu, Lizhi Chen, Yuan Li, Laixin Xia, Shan Xiao
Summary: This study developed a method to accurately detect allele-specific m(6)A and identified genetic variants associated with common diseases. It reveals the important role of m(6)A and genetics in human health and disease.
Review
Biochemistry & Molecular Biology
Tomasz W. Turowski, Magdalena Boguta
Summary: RNAPI and RNAPIII are multi-heterogenic protein complexes specialized in transcribing highly abundant non-coding RNAs, more complex than RNAPII synthesizing mRNAs. They share associated subcomplexes formed by specific subunits in yeast and establish an assembly platform co-translationally during the synthesis of the Rpb10 subunit.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Biology
Richard J. White, Eirinn Mackay, Stephen W. Wilson, Elisabeth M. Busch-Nentwich
Summary: In zebrafish, differentially expressed genes are often over-represented on the same chromosome as the mutation, due to different levels of expression of alleles from different genetic backgrounds. This has implications for interpreting the results and pathways in RNA-seq experiments.
Article
Neurosciences
Julia Udden, Annika Hulten, Katarina Bendtz, Zachary Mineroff, Katerina S. Kucera, Arianna Vino, Evelina Fedorenko, Peter Hagoort, Simon E. Fisher
JOURNAL OF NEUROSCIENCE
(2019)
Article
Oncology
Adriana C. Rodriguez, Jeffery M. Vahrenkamp, Kristofer C. Berrett, Kathleen A. Clark, Katrin P. Guillen, Sandra D. Scherer, Chieh-Hsiang Yang, Bryan E. Welm, Margit M. Janat-Amsbury, Barbara J. Graves, Jason Gertz
Correction
Biology
Amanda K. Tilot, Arianna Vino, Katerina S. Kucera, Duncan A. Carmichael, Loes van den Heuvel, Joery den Hoed, Anton V. Sidoroff-Dorso, Archie Campbell, David J. Porteous, Beate St Pourcain, Tessa M. van Leeuwen, Jamie Ward, Romke Rouw, Julia Simner, Simon E. Fisher
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2020)
Article
Biochemical Research Methods
Jordan A. Berg, Jonathan R. Belyeu, Jeffrey T. Morgan, Yeyun Ouyang, Alex J. Bott, Aaron R. Quinlan, Jason Gertz, Jared Rutter
PLOS COMPUTATIONAL BIOLOGY
(2020)
Article
Oncology
Abbie S. Ireland, Alexi M. Micinski, David W. Kastner, Bingqian Guo, Sarah J. Wait, Kyle B. Spainhower, Christopher C. Conley, Opal S. Chen, Matthew R. Guthrie, Danny Soltero, Yi Qiao, Xiaomeng Huang, Szabolcs Tarapcsak, Siddhartha Devarakonda, Milind D. Chalishazar, Jason Gertz, Justin C. Moser, Gabor Marth, Sonam Puri, Benjamin L. Witt, Benjamin T. Spike, Trudy G. Oliver
Article
Biochemistry & Molecular Biology
Julia B. Carleton, Matthew Ginley-Hidinger, Kristofer C. Berrett, Ryan M. Layer, Aaron R. Quinlan, Jason Gertz
NUCLEIC ACIDS RESEARCH
(2020)
Article
Cell & Tissue Engineering
Niloofar Farhang, Bryton Davis, Jacob Weston, Matthew Ginley-Hidinger, Jason Gertz, Robby D. Bowles
TISSUE ENGINEERING PART A
(2020)
Article
Multidisciplinary Sciences
Samuel Byiringiro, Rex Wong, Jenae Logan, Deogratias Kaneza, Joseph Gitera, Sharon Umutesi, Catherine M. Kirk
Summary: The study found that admitting a newborn to the NCU in rural Rwanda is stressful for parents and caregivers, but there are also positive aspects that help mothers adapt to the environment. Effective communication and active involvement can improve the parents' experience in the NCU.
Article
Microbiology
Jean H. H. Kim, Veronica Robles, Kristin E. D. Weimer, Lisa H. M. Gehtland, Katerina S. S. Kucera
Summary: The implementation of cCMV screening in public health programs is hindered by challenges such as limited specimen availability and an insufficiently sensitive DBS-based assay. Efforts have been made to improve the currently available DBS-based method in order to increase its feasibility in newborn screening programs. Evaluation: 7 out of 10.
MICROBIOLOGY SPECTRUM
(2023)
Article
Genetics & Heredity
Paul Dantonio, Norma P. P. Tavakoli, Brooke Migliore, Elizabeth McCown, Timothy Lim, Sunju Park, Michele Caggana, Katerina S. S. Kucera, Han Phan, Natalie Street, Konstantinos Petritis, Robert F. F. Vogt
Summary: Pilot studies for newborn bloodspot screening to detect Duchenne Muscular Dystrophy (DMD) are being conducted in the US and RTI International. The US CDC NSQAP provided DBS reference materials with different levels of CK-MM for these studies, and the results from each laboratory correlated well with the CK-MM levels. This set of reference materials allows quality assessment of CK-MM levels in both normal and DMD-affected newborns.
INTERNATIONAL JOURNAL OF NEONATAL SCREENING
(2023)
Article
Genetics & Heredity
Katerina S. Kucera, Beth Lincoln Boyea, Brooke Migliore, Sarah Nelson Potter, Veronica R. Robles, Oksana Kutsa, Heidi Cope, Katherine C. Okoniewski, Anne Wheeler, Catherine W. Rehder, Edward C. Smith, Holly L. Peay
Summary: Screening for elevated CK-MM levels in dried blood spots is a feasible method to identify newborns with DMD. Including specific cutoffs, repeat testing, and genetic sequencing can improve the accuracy and sensitivity of screening.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Brooke Migliore, Linran Zhou, Martin Duparc, Veronica Robles, Catherine Rehder, Holly Peay, Katerina Kucera
Summary: Duchenne Muscular Dystrophy (DMD) is a fatal genetic disorder that can be screened using the muscle enzyme creatine kinase-MM (CK-MM). This study evaluated the accuracy and residual effects of the CK-MM kit and analyzed the impact of humidity on CK-MM degradation in stored samples. The findings suggest that reducing humidity can mitigate CK-MM degradation. Assessment of DBS shipping and storage conditions is recommended prior to DMD screening.
INTERNATIONAL JOURNAL OF NEONATAL SCREENING
(2022)
Meeting Abstract
Endocrinology & Metabolism
Holly Peay, Katerina Kucera, Beth Boyea, Edward Smith, Brooke Migliore, Martin Duparc, Catherine Rehder, Don Bailey
MOLECULAR GENETICS AND METABOLISM
(2021)
Article
Genetics & Heredity
Katerina S. Kucera, Jennifer L. Taylor, Veronica R. Robles, Kristin Clinard, Brooke Migliore, Beth Lincoln Boyea, Katherine C. Okoniewski, Martin Duparc, Catherine W. Rehder, Scott M. Shone, Zheng Fan, Melissa Raspa, Holly L. Peay, Anne C. Wheeler, Cynthia M. Powell, Donald B. Bailey, Lisa M. Gehtland
Summary: Prior to statewide implementation of newborn screening for spinal muscular atrophy in North Carolina, USA, we conducted voluntary screening through the Early Check research study. During the study period from October 2018 to December 2020, we enrolled 12,065 newborns, identified one severe early onset SMA case and one false positive result, and evaluated screening methods to ensure robustness. Prenatal enrollment led to faster result return, but postnatal enrollment still allowed for early treatment opportunities within a reasonable timeframe.
INTERNATIONAL JOURNAL OF NEONATAL SCREENING
(2021)
Article
Public, Environmental & Occupational Health
Sandra Isano, Rex Wong, Jenae Logan, Soha El-Halabi, Ziad El-Khatib
PREVENTIVE MEDICINE REPORTS
(2020)