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Your search keyword '"Zagore, Leah"' showing total 3 results
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3 results on '"Zagore, Leah"'

1. Adaptive translational pausing is a hallmark of the cellular response to severe environmental stress

Author

Jobava, Raul, Mao, Yuanhui, Guan, Bo-Jhih, Hu, Di, Krokowski, Dawid, Chen, Chien-Wen, Shu, Xin Erica, Chukwurah, Evelyn, Wu, Jing, Gao, Zhaofeng, Zagore, Leah L., Merrick, William C., Trifunovic, Aleksandra, Hsieh, Andrew C., Valadkhan, Saba, Zhang, Youwei, Qi, Xin, Jankowsky, Eckhard, Topisirovic, Ivan, Licatalosi, Donny D., Qian, Shu-Bing, Hatzoglou, Maria, Jobava, Raul, Mao, Yuanhui, Guan, Bo-Jhih, Hu, Di, Krokowski, Dawid, Chen, Chien-Wen, Shu, Xin Erica, Chukwurah, Evelyn, Wu, Jing, Gao, Zhaofeng, Zagore, Leah L., Merrick, William C., Trifunovic, Aleksandra, Hsieh, Andrew C., Valadkhan, Saba, Zhang, Youwei, Qi, Xin, Jankowsky, Eckhard, Topisirovic, Ivan, Licatalosi, Donny D., Qian, Shu-Bing, and Hatzoglou, Maria

Abstract

To survive, mammalian cells must adapt to environmental challenges. While the cellular response to mild stress has been widely studied, how cells respond to severe stress remains unclear. We show here that under severe hyperosmotic stress, cells enter a transient hibernation-like state in anticipation of recovery. We demonstrate this adaptive pausing response (APR) is a coordinated cellular response that limits ATP supply and consumption through mitochondrial fragmentation and widespread pausing of mRNA translation. This pausing is accomplished by ribosome stalling at translation initiation codons, which keeps mRNAs poised to resume translation upon recovery. We further show that recovery from severe stress involves ISR (integrated stress response) signaling that permits cell cycle progression, resumption of growth, and reversal of mitochondria fragmentation. Our findings indicate that cells can respond to severe stress via a hibernation-like mechanism that preserves vital elements of cellular function under harsh environmental conditions.

Published
2021

2. DAZL Regulates Germ Cell Survival through a Network of PolyA-Proximal mRNA Interactions.

Author

Zagore LL, Sweet TJ, Hannigan MM, Weyn-Vanhentenryck SM, Jobava R, Hatzoglou M, Zhang C, and Licatalosi DD

Subjects
3' Untranslated Regions genetics, 5' Untranslated Regions genetics, Aging, Animals, Base Sequence, Binding Sites, Cell Cycle genetics, Cell Survival, Female, Gene Expression Regulation, Gene Regulatory Networks, Male, Mice, Inbred C57BL, Protein Binding, RNA, Messenger genetics, RNA, Messenger metabolism, Testis metabolism, Transcription, Genetic, Transcriptome genetics, Germ Cells cytology, Germ Cells metabolism, Poly A metabolism, RNA-Binding Proteins metabolism
Abstract

The RNA binding protein DAZL is essential for gametogenesis, but its direct in vivo functions, RNA targets, and the molecular basis for germ cell loss in Dazl-null mice are unknown. Here, we mapped transcriptome-wide DAZL-RNA interactions in vivo, revealing DAZL binding to thousands of mRNAs via polyA-proximal 3' UTR interactions. In parallel, fluorescence-activated cell sorting and RNA-seq identified mRNAs sensitive to DAZL deletion in male germ cells. Despite binding a broad set of mRNAs, integrative analyses indicate that DAZL post-transcriptionally controls only a subset of its mRNA targets, namely those corresponding to a network of genes that are critical for germ cell proliferation and survival. In addition, we provide evidence that polyA sequences have key roles in specifying DAZL-RNA interactions across the transcriptome. Our results reveal a mechanism for DAZL-RNA binding and illustrate that DAZL functions as a master regulator of a post-transcriptional mRNA program essential for germ cell survival., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Published
2018
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3. Ptbp2 Controls an Alternative Splicing Network Required for Cell Communication during Spermatogenesis.

Author

Hannigan MM, Zagore LL, and Licatalosi DD

Subjects
Animals, Cell Communication, Cell Polarity, Exons, Female, Gene Ontology, Male, Meiosis, Mice, Inbred C57BL, Sertoli Cells physiology, Sertoli Cells ultrastructure, Alternative Splicing, Nerve Tissue Proteins physiology, Polypyrimidine Tract-Binding Protein physiology, Spermatogenesis, Spermatozoa physiology
Abstract

Alternative splicing has essential roles in development. Remarkably, spermatogenic cells express more alternatively spliced RNAs compared to most whole tissues; however, regulation of these RNAs remains unclear. Here, we characterize the alternative splicing landscape during spermatogenesis and reveal an essential function for the RNA-binding protein Ptbp2 in this highly regulated developmental program. We found that Ptbp2 controls a network of genes involved in cell adhesion, migration, and polarity, suggesting that splicing regulation by Ptbp2 is critical for germ cell communication with Sertoli cells (multifunctional somatic cells necessary for spermatogenesis). Indeed, Ptbp2 ablation in germ cells resulted in disorganization of the filamentous actin (F-actin) cytoskeleton in Sertoli cells, indicating that alternative splicing regulation is necessary for cellular crosstalk during germ cell development. Collectively, the data delineate an alternative splicing regulatory network essential for spermatogenesis, the splicing factor that controls it, and its biological importance in germ-Sertoli communication., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Published
2017
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