Article
Multidisciplinary Sciences
Leo Shen, Lauren Pugsley, Regina Cencic, HanChen Wang, Francis Robert, Sai Kiran Naineni, Ananya Sahni, Genevieve Morin, Wenhan Zhang, Anastasia Nijnik, John A. Porco, David Langlais, Sidong Huang, Jerry Pelletier
Summary: The article discusses the mechanism of action and resistance mechanisms of eukaryotic translation initiation inhibitors rocaglates, identifying transcription factors FOXP3 and NR1I3 as potent modifiers of rocaglate response. Additionally, FOXP3 and NR1I3 confer a multi-drug resistant phenotype that can be reversed by inhibiting Pgp, suggesting a potential therapeutic combination strategy.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Nikki M. McCormack, Mahlet B. Abera, Eveline S. Arnold, Rebecca M. Gibbs, Scott E. Martin, Eugen Buehler, Yu-Chi Chen, Lu Chen, Kenneth H. Fischbeck, Barrington G. Burnett
Summary: The study uncovered pathways regulating SMN expression, providing new insights for treating SMA.
Article
Microbiology
David W. Morgens, Divya Nandakumar, Allison L. Didychuk, Kevin J. Yang, Britt A. Glaunsinger
Summary: This study demonstrates the use of CRISPR/Cas9 to rapidly create and screen thousands of mutant viruses in Kaposi's sarcoma-associated herpesvirus (KSHV). By analyzing the expression of viral genes in these mutant viruses, a novel required gene was identified and its specific function was characterized using targeted deep viral sequencing.
Article
Biology
Sahil H. Shah, Lucio M. Schiapparelli, Yuanhui Ma, Satoshi Yokota, Melissa Atkins, Xin Xia, Evan G. Cameron, Thanh Huang, Sarah Saturday, Catalina B. Sun, Cara Knasel, Seth Blackshaw, John R. Yates, Hollis T. Cline, Jeffrey L. Goldberg
Summary: Many neurons in the adult central nervous system degenerate and die after injury, and early changes in axon protein transport have not been quantified in disease models. This study identified transport failure of the motor protein Kif5a as a cause of RGC neurodegeneration and characterized its effects on axon transport in mice. Knockout of Kif5a in RGCs resulted in progressive RGC degeneration even in the absence of injury.
Article
Multidisciplinary Sciences
Jianting Shi, Xun Wu, Ziyi Wang, Fang Li, Yujiao Meng, Rebecca M. Moore, Jian Cui, Chenyi Xue, Katherine R. Croce, Arif Yurdagul, John G. Doench, Wei Li, Konstantinos S. Zarbalis, Ira Tabas, Ai Yamamoto, Hanrui Zhang
Summary: This study identified WDFY3 as a novel regulator of efferocytosis through a genome-wide CRISPR screen, revealing its role in promoting LC3 lipidation and lysosomal acidification for the degradation of apoptotic cell components.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Tatyana G. Kahn, Mikhail Savitsky, Chikuan Kuong, Caroline Jacquier, Giacomo Cavalli, Jia-Ming Chang, Yuri B. Schwartz
Summary: Drosophila insulators are DNA elements that regulate gene expression by limiting chromatin contacts. By mapping chromatin contacts in Drosophila cells without key insulator proteins CTCF and Cp190, we discovered hundreds of insulator elements. Our findings suggest that Drosophila insulators play a minor role in overall genome folding but have a local impact on chromatin contacts. Our insulator catalog is an important resource for studying genome folding mechanisms.
Article
Genetics & Heredity
Johnathan Rylee, Simpla Mahato, John Aldrich, Emma Bergh, Brandon Sizemore, Lauren E. Feder, Shaun Grega, Kennedy Helms, Megan Maar, Steven G. Britt, Andrew C. Zelhof
Summary: This study identified additional molecules and cellular pathways required for the differentiation and organization of Drosophila rhabdomeric photoreceptors through an RNAi screen, revealing potential new regulatory molecules and pathways.
G3-GENES GENOMES GENETICS
(2022)
Article
Genetics & Heredity
Rebecca A. S. Palu, Katie G. Owings, John G. Garces, Audrey Nicol
Summary: Variation in the onset, progression, and severity of symptoms associated with metabolic disorders such as diabetes impairs the diagnosis and treatment of at-risk patients. In this study, using a fruit fly model, the researchers identified genetic variation that influences hyperglycemia and discovered genes related to glucose metabolism, insulin signaling, neuronal signaling, and innate immune response. Decreasing the expression of certain candidate genes suppressed hyperglycemia, suggesting their potential as therapeutic targets.
G3-GENES GENOMES GENETICS
(2022)
Article
Cell Biology
Fang Cao, Yunpeng Jiang, Lin Chang, Hongzhen Du, De Chang, Chunxiao Pan, Xiaozheng Huang, Donglin Yu, Mi Zhang, Yongna Fan, Xiaocui Bian, Kailong Li
Summary: Pancreatic cancer is characterized by early metastasis and limited response to current therapies. Through a genetic screening platform, YWHAZ has been identified as a key regulator of pancreatic cancer metastasis. Overexpression of YWHAZ promotes cell migration and invasion, and is associated with poor prognosis in pancreatic cancer patients.
CELL DEATH & DISEASE
(2023)
Article
Genetics & Heredity
Ana Lopez-Varea, Cristina M. Ostale, Patricia Vega-Cuesta, Ana Ruiz-Gomez, Maria F. Organista, Mercedes Martin, Covadonga F. Hevia, Cristina Molnar, Jesus de Celis, Joaquim Culi, Nuria Esteban, Jose F. de Celis
Summary: Through knocking down genes targeting Drosophila protein-coding genes in adult wing, critical genes affecting wing development were identified and further classified and analyzed for their functions and expressions, offering valuable information for a deeper understanding of the biological processes involved in wing formation.
G3-GENES GENOMES GENETICS
(2021)
Article
Multidisciplinary Sciences
Zhifen Zhou, Yujing Li, Huimin Xu, Xiaowei Xie, Zibin He, Song Lin, Ruofei Li, Shouheng Jin, Jun Cui, Hai Hu, Feng Liu, Su Wu, Wenbin Ma, Zhou Songyang
Summary: This study identified multiple positive regulators, including the E3 ligase DTX2, through an inducible CRISPR/Cas9 KO screen. Depletion of DTX2 in telomerase-positive cancer cells resulted in downregulation of hTERT transcription and telomerase activity, leading to progressive telomere shortening, growth arrest, and increased apoptosis. BioID analysis revealed that DTX2 interacts with multiple transcription factors, with NFIC functioning cooperatively with DTX2 to promote hTERT transcription. Further investigation demonstrated that DTX2 mediates K63-linked ubiquitination of NFIC, which enhances NFIC binding to the hTERT promoter and increases hTERT expression.
Article
Multidisciplinary Sciences
Fan Xia, Yuan Ma, Kangfu Chen, Bill Duong, Sharif Ahmed, Randy Atwal, David Philpott, Troy Ketela, Jennifer Pantea, Sichun Lin, Stephane Angers, Shana O. Kelley
Summary: In this study, CTCs from mouse xenograft were used for an in vivo genome-wide CRISPR knockout screen, and SLIT2 gene was identified as the most significantly represented gene knockout in the CTC population, showing highly metastatic cells.
Article
Biochemistry & Molecular Biology
Lounis Yakhou, Anaelle Azogui, Nikhil Gupta, Julien Richard Albert, Fumihito Miura, Laure Ferry, Kosuke Yamaguchi, Sarah Battault, Pierre Therizols, Frederic Bonhomme, Elouan Bethuel, Arpita Sarkar, Maxim V. C. Greenberg, Paola B. Arimondo, Gael Cristofari, Olivier Kirsh, Takashi Ito, Pierre-Antoine Defossez
Summary: Epigenetic mechanisms play crucial roles in establishing and maintaining cellular identities in mammals. They regulate the expression of genes, transposable elements, and chromatin structures, and are essential for mammalian development. Bivalent promoters are particularly important during differentiation and development. BEND3 has been identified as a regulator of bivalent promoters, and its absence leads to genome-wide DNA methylation gains and reduced DNA hydroxymethylation, suggesting its direct and indirect roles in chromatin regulation.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Dan Li, Jihong Yang, Vikas Malik, Yuting Huang, Xin Huang, Hongwei Zhou, Jianlong Wang
Summary: RNA helicase eIF4A3 plays a crucial role in maintaining pluripotency of stem cells by post-transcriptionally controlling the cell cycle, particularly the efficient nuclear export of Ccnb1 mRNA.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Cell Biology
Shao-Yen Kao, Elena Nikonova, Sabrina Chaabane, Albiona Sabani, Alexandra Martitz, Anja Wittner, Jakob Heemken, Tobias Straub, Maria L. Spletter
Summary: Proper regulation of RNA processing is crucial for muscle development and contractile ability, with RNA binding proteins playing a key role in alternative splicing. Disruption of splicing is associated with muscle diseases and altered by exercise and aging. Drosophila is a valuable model to study the role of RBPs in myogenesis and to investigate the impact of splicing defects on myofibril development.