Interactome analysis illustrates diverse gene regulatory processes associated with LIN28A in human iPS cell-derived neural progenitor cells
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
Affiliations
Nam-Kyung Yu
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
Daniel B. McClatchy
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
Jolene K. Diedrich
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
Sarah Romero
Department 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
Jun-Hyeok Choi
Neurobiology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA
Salvador Martínez-Bartolomé
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
Claire M. Delahunty
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
Alysson R. Muotri
Department 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, USA
John R. Yates, III
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA; Corresponding author
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.
