Article
Cell Biology
Jia Fei, Jun Xu, Ziwei Li, Kevin Xu, Dong Wang, George A. Kassavetis, James T. Kadonaga
Summary: NDF is a transcription elongation factor that binds to Pol II and enhances gene expression elongation by a different mechanism than TFIIS.
GENES & DEVELOPMENT
(2022)
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
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
Biochemistry & Molecular Biology
Izabela Rudzinska, Malgorzata Ciesla, Tomasz W. Turowski, Alicja Armatowska, Ewa Lesniewska, Magdalena Boguta
Summary: The study showed that the rpc128-1007 mutant disrupts Pol III assembly, affecting mRNA expression levels, particularly through modulation of the general transcription factor Gcn4. Additionally, regardless of suppressor genes, the rpc128-1007 mutation leads to a slight increase in the expression of ribosome biogenesis genes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Samuel H. Keller, Hao Deng, Bomyi Lim
Summary: This study examines how enhancers, promoters, and gene body composition affect the rate of RNA Pol II elongation through a live imaging assay in single cells. The research findings reveal that promoters and exonic gene lengths do not impact the elongation rate, while enhancers and the presence of long introns have a significant effect on the speed of RNA Pol II movement across genes. Additionally, it was observed that RNA Pol II elongation rate accelerates after the transcriptional onset of nuclear cycle 14 in Drosophila embryos. These findings provide insights into the mechanisms that regulate the dynamic RNA Pol II elongation rate.
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)
Review
Biochemistry & Molecular Biology
Niko Linzer, Alexis Trumbull, Rukiye Nar, Matthew D. Gibbons, David T. Yu, John Strouboulis, Joerg Bungert
Summary: TFII-I, a key transcription factor, plays crucial roles in regulating Pol II transcription at the stages of initiation and elongation by interacting with various co-regulators and influencing transcription positively or negatively. Its expression changes are associated with a range of diseases and developmental processes, highlighting its important role in gene regulation.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Multidisciplinary Sciences
Amit K. Singh, Qingrong Chen, Cu Nguyen, Daoud Meerzaman, Dinah S. Singer
Summary: Cohesin plays a role in regulating alternative splicing by interacting with splicing factors and influencing splicing patterns. Mutations in cohesin are associated with distinct splicing patterns in acute myeloid leukemia, and cohesin interacts with another splicing regulator, BRD4, to generate unique splicing patterns. These findings provide insights into the role of cohesin in both normal and leukemic cells and its contribution to human disease.
Article
Biochemistry & Molecular Biology
Yuanjun Li, Jie Huang, Junyi Zhu, Lijun Bao, Hui Wang, Yongpeng Jiang, Kai Tian, Rui Wang, Haonan Zheng, WenJia Duan, Weifeng Lai, Xiao Yi, Yi Zhu, Tiannan Guo, Xiong Ji
Summary: The study revealed that different RNA Pol II subunits play distinct roles in transcription regulation, with a preference for RNA processing. Depletion of different RNA Pol II subunits leads to differential gene expression, involving diverse biological functions.
Article
Cell Biology
Sezen Meydan, Gessica C. Barros, Vanessa Simoes, Lana Harley, Blanche K. Cizubu, Nicholas R. Guydosh, Gustavo M. Silva
Summary: Under oxidative stress conditions, the E2 ubiquitin conjugase Rad6 mediates K63-linked ubiquitination of ribosomes, leading to ribosome pausing at specific amino acid motifs and ribosome collisions. These redoxpausing signatures are independent of the ribosome-associated quality control (RQC) pathway and Rad6 is also required to inhibit overall translation during oxidative stress, resulting in increased expression of antioxidant genes. The absence of Rad6 affects translation during oxidative stress and impacts the activation of the integrated stress response (ISR) pathway.
Article
Immunology
Jiayao Ou, Xiaoxing Guan, Jiali Wang, Tianjiao Wang, Bin Zhang, Rong Li, Huji Xu, Xiaoyu Hu, Xue-Kun Guo
Summary: The NELF complex plays a critical role in maintaining epithelial homeostasis in intestinal epithelial cells by sustaining expression of genes related to junctional integrity. Lack of NELF results in impaired barrier integrity and exacerbated inflammation in the intestine, highlighting the importance of elongation in defining the IEC transcriptome.
MUCOSAL IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Preeti Khan, Priyabrata Singha, Ronita Chaudhuri
Summary: This study shows that there is crosstalk between deacetylation of H4K16 and acetylation of H3K56, which promotes the progression of RNA polymerase II through the gene body in Saccharomyces cerevisiae. The results indicate that deacetylation of H4K16 precedes and induces H3K56 acetylation. The recruitment of Rtt109, the histone acetyltransferase responsible for H3K56 acetylation, depends on H4K16 deacetylation. These modifications play a crucial role in the successful functioning of RNA polymerase II during active transcription.
MOLECULAR AND CELLULAR BIOLOGY
(2023)
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
Chengli Fang, Yu Zhang
Summary: MerR family transcription factors modulate gene expression in bacteria, functioning as transcription repressors under normal circumstances but rapidly transforming to transcription activators under cellular triggers. They bind in a unique mechanism in the long spacer of the promoter region, regulating transcription activity.
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
(2022)
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
Biochemistry & Molecular Biology
Benjamin C. Kaster, Kevin C. Knippa, Craig D. Kaplan, David O. Peterson
JOURNAL OF BIOLOGICAL CHEMISTRY
(2016)
Article
Biochemistry & Molecular Biology
Indranil Malik, Chenxi Qiu, Thomas Snavely, Craig D. Kaplan
NUCLEIC ACIDS RESEARCH
(2017)
Article
Genetics & Heredity
Nairita Maitra, Jayamani Anandhakumar, Heidi M. Blank, Craig D. Kaplan, Michael Polymenis
G3-GENES GENOMES GENETICS
(2019)
Review
Biochemical Research Methods
Chenxi Qiu, Craig D. Kaplan
Article
Biology
Zhijie Chen, Ronen Gabizon, Aidan I. Brown, Antony Lee, Aixin Song, Cesar Diaz-Celis, Craig D. Kaplan, Elena F. Koslover, Tingting Yao, Carlos Bustamante
Article
Biochemistry & Molecular Biology
Xueyuan Leng, Maxim Iyanov, Peter Kindgren, Indranil Malik, Axel Thieffry, Peter Brodersen, Albin Sandelin, Craig D. Kaplan, Sebastian Marquardt
Article
Biochemistry & Molecular Biology
Sarah J. Hainer, Craig D. Kaplan
Article
Biochemistry & Molecular Biology
Natalie M. Garza, Aaron T. Griffin, Mohammad Zulkifli, Chenxi Qiu, Craig D. Kaplan, Vishal M. Gohil
Summary: This study identified novel genetic regulators of mitochondrial copper homeostasis through a genome-wide screen, including subunits of the AP-3 complex and components of the cellular pH-sensing pathway. These genes impact vacuolar acidity, which in turn perturbs mitochondrial copper homeostasis and CcO function. The study provides insights into how vacuolar pH affects mitochondrial respiration through copper homeostasis.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Trevor van Eeuwen, Yoonjung Shim, Hee Jong Kim, Tingting Zhao, Shrabani Basu, Benjamin A. Garcia, Craig D. Kaplan, Jung-Hyun Min, Kenji Murakami
Summary: The study presents a cryo-EM structure of an NER initiation complex, showing how the XPC-RAD23B-CETN2 complex and TFIIH complex work together to recognize and verify DNA lesions. This interaction allows for unwinding of DNA and delivery of damaged strands for subsequent scanning and verification.
NATURE COMMUNICATIONS
(2021)
Article
Biology
Tingting Zhao, Irina O. Vvedenskaya, William K. M. Lai, Shrabani Basu, B. Franklin Pugh, Bryce E. Nickels, Craig D. Kaplan
Summary: Research has shown that Ssl2 plays a crucial role in promoter scanning by controlling TSS selection through regulating processivity rather than rate, possibly related to its ATPase activity. The study reveals the genetic interaction patterns of ssl2 alleles and their impact on the promoter scanning process and TSS selection.
Letter
Multidisciplinary Sciences
Leonid Kruglyak, Andreas Beyer, Joshua S. Bloom, Jan Grossbach, Tami D. Lieberman, Christopher P. Mancuso, Matthew S. Rich, Gavin Sherlock, Craig D. Kaplan
Article
Biochemical Research Methods
Bercem Dutagaci, Bingbing Duan, Chenxi Qiu, Craig D. Kaplan, Michael Feig
Summary: The trigger loop (TL) is a highly conserved active site domain that plays a crucial role in catalysis and fidelity of multisubunit RNA polymerases. This study used molecular dynamics simulation (MD) and machine learning (ML) techniques to investigate TL mutations in Saccharomyces cerevisiae RNA Polymerase II (Pol II). The results showed that ML could predict the phenotypes of TL mutants with a high correlation. While it was challenging to incorporate MD data into machine learning, a variational auto-encoder model based on the MD data successfully clustered mutants based on structural details.
PLOS COMPUTATIONAL BIOLOGY
(2023)
Article
Genetics & Heredity
Adam W. Hansen, Payal Arora, Michael M. Khayat, Leah J. Smith, Andrea M. Lewis, Linda Z. Rossetti, Joy Jayaseelan, Ingrid Cristian, Devon Haynes, Stephanie DiTroia, Naomi Meeks, Mauricio R. Delgado, Jill A. Rosenfeld, Lynn Pais, Susan M. White, Qingchang Meng, Davut Pehlivan, Pengfei Liu, Marie-Claude Gingras, Michael F. Wangler, Donna M. Muzny, James R. Lupski, Craig D. Kaplan, Richard A. Gibbs
Summary: The study reported 12 individuals with variants in POLR2A, showing phenotypes such as ataxia, joint hypermobility, short stature, skin abnormalities, congenital cardiac abnormalities, immune system abnormalities. Most patients also had epilepsy, while the occurrence of hypotonia was lower.
HUMAN GENETICS AND GENOMICS ADVANCES
(2021)
Article
Biotechnology & Applied Microbiology
Chenxi Qiu, Huiyan Jin, Irina Vvedenskaya, Jordi Abante Llenas, Tingting Zhao, Indranil Malik, Alex M. Visbisky, Scott L. Schwartz, Ping Cui, Pavel Cabart, Kang Hoo Han, William K. M. Lai, Richard P. Metz, Charles D. Johnson, Sing-Hoi Sze, B. Franklin Pugh, Bryce E. Nickels, Craig D. Kaplan
Meeting Abstract
Biochemistry & Molecular Biology
Craig D. Kaplan
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)