Interactome analysis illustrates diverse gene regulatory processes associated with LIN28A in human iPS cell-derived neural progenitor cells

Summary: A single protein can be multifaceted depending on the cellular contexts and interacting molecules. LIN28A is an RNA-binding protein that governs developmental timing, cellular proliferation, differentiation, stem cell pluripotency, and metabolism. In addition to its best-known roles in micr...

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Main Authors: Nam-Kyung Yu, Daniel B. McClatchy, Jolene K. Diedrich, Sarah Romero, Jun-Hyeok Choi, Salvador Martínez-Bartolomé, Claire M. Delahunty, Alysson R. Muotri, John R. Yates, III
Format: Article
Language:English
Published: Elsevier 2021-11-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004221012906
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author Nam-Kyung Yu
Daniel B. McClatchy
Jolene K. Diedrich
Sarah Romero
Jun-Hyeok Choi
Salvador Martínez-Bartolomé
Claire M. Delahunty
Alysson R. Muotri
John R. Yates, III
author_facet Nam-Kyung Yu
Daniel B. McClatchy
Jolene K. Diedrich
Sarah Romero
Jun-Hyeok Choi
Salvador Martínez-Bartolomé
Claire M. Delahunty
Alysson R. Muotri
John R. Yates, III
author_sort Nam-Kyung Yu
collection DOAJ
description Summary: A single protein can be multifaceted depending on the cellular contexts and interacting molecules. LIN28A is an RNA-binding protein that governs developmental timing, cellular proliferation, differentiation, stem cell pluripotency, and metabolism. In addition to its best-known roles in microRNA biogenesis, diverse molecular roles have been recognized. In the nervous system, LIN28A is known to play critical roles in proliferation and differentiation of neural progenitor cells (NPCs). We profiled the endogenous LIN28A-interacting proteins in NPCs differentiated from human induced pluripotent stem (iPS) cells using immunoprecipitation and liquid chromatography-tandem mass spectrometry. We identified over 500 LIN28A-interacting proteins, including 156 RNA-independent interactors. Functions of these proteins span a wide range of gene regulatory processes. Prompted by the interactome data, we revealed that LIN28A may impact the subcellular distribution of its interactors and stress granule formation upon oxidative stress. Overall, our analysis opens multiple avenues for elaborating molecular roles and characteristics of LIN28A.
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spelling doaj.art-4350b3b7587746e6bd8c1c81b0bf89e62022-12-21T20:46:02ZengElsevieriScience2589-00422021-11-012411103321Interactome analysis illustrates diverse gene regulatory processes associated with LIN28A in human iPS cell-derived neural progenitor cellsNam-Kyung Yu0Daniel B. McClatchy1Jolene K. Diedrich2Sarah Romero3Jun-Hyeok Choi4Salvador Martínez-Bartolomé5Claire M. Delahunty6Alysson R. Muotri7John R. Yates, III8Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Pediatrics/Rady Children’s Hospital San Diego, Department of Cellular & Molecular Medicine, School of Medicine, University of California, San Diego, San Diego, CA 92037, USANeurobiology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USADepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Pediatrics/Rady Children’s Hospital San Diego, Department of Cellular & Molecular Medicine, School of Medicine, University of California, San Diego, San Diego, CA 92037, USA; Stem Cell Program, Center for Academic Research and Training in Anthropogeny (CARTA), Archealization Center (ArchC), Kavli Institute for Brain and Mind, La Jolla, CA 92037, USADepartment of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA; Corresponding authorSummary: A single protein can be multifaceted depending on the cellular contexts and interacting molecules. LIN28A is an RNA-binding protein that governs developmental timing, cellular proliferation, differentiation, stem cell pluripotency, and metabolism. In addition to its best-known roles in microRNA biogenesis, diverse molecular roles have been recognized. In the nervous system, LIN28A is known to play critical roles in proliferation and differentiation of neural progenitor cells (NPCs). We profiled the endogenous LIN28A-interacting proteins in NPCs differentiated from human induced pluripotent stem (iPS) cells using immunoprecipitation and liquid chromatography-tandem mass spectrometry. We identified over 500 LIN28A-interacting proteins, including 156 RNA-independent interactors. Functions of these proteins span a wide range of gene regulatory processes. Prompted by the interactome data, we revealed that LIN28A may impact the subcellular distribution of its interactors and stress granule formation upon oxidative stress. Overall, our analysis opens multiple avenues for elaborating molecular roles and characteristics of LIN28A.http://www.sciencedirect.com/science/article/pii/S2589004221012906Gene networkMolecular neuroscienceOmicsStem cells research
spellingShingle Nam-Kyung Yu
Daniel B. McClatchy
Jolene K. Diedrich
Sarah Romero
Jun-Hyeok Choi
Salvador Martínez-Bartolomé
Claire M. Delahunty
Alysson R. Muotri
John R. Yates, III
Interactome analysis illustrates diverse gene regulatory processes associated with LIN28A in human iPS cell-derived neural progenitor cells
iScience
Gene network
Molecular neuroscience
Omics
Stem cells research
title Interactome analysis illustrates diverse gene regulatory processes associated with LIN28A in human iPS cell-derived neural progenitor cells
title_full Interactome analysis illustrates diverse gene regulatory processes associated with LIN28A in human iPS cell-derived neural progenitor cells
title_fullStr Interactome analysis illustrates diverse gene regulatory processes associated with LIN28A in human iPS cell-derived neural progenitor cells
title_full_unstemmed Interactome analysis illustrates diverse gene regulatory processes associated with LIN28A in human iPS cell-derived neural progenitor cells
title_short Interactome analysis illustrates diverse gene regulatory processes associated with LIN28A in human iPS cell-derived neural progenitor cells
title_sort interactome analysis illustrates diverse gene regulatory processes associated with lin28a in human ips cell derived neural progenitor cells
topic Gene network
Molecular neuroscience
Omics
Stem cells research
url http://www.sciencedirect.com/science/article/pii/S2589004221012906
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