title: The CELF1 RNA-Binding Protein Regulates Decay of Signal Recognition Particle mRNAs and Limits Secretion in Mouse Myoblasts.
abstract: We previously identified several mRNAs encoding components of the secretory pathway, including signal recognition particle (SRP) subunit mRNAs, among transcripts associated with the RNA-binding protein CELF1. Through immunoprecipitation of RNAs crosslinked to CELF1 in myoblasts and in vitro binding assays using recombinant CELF1, we now provide evidence that CELF1 directly binds the mRNAs encoding each of the subunits of the SRP. Furthermore, we determined the half-lives of the Srp transcripts in control and CELF1 knockdown myoblasts. Our results indicate CELF1 is a destabilizer of at least five of the six Srp transcripts and that the relative abundance of the SRP proteins is out of balance when CELF1 is depleted. CELF1 knockdown myoblasts exhibit altered secretion of a luciferase reporter protein and are impaired in their ability to migrate and close a wound, consistent with a defect in the secreted extracellular matrix. Importantly, similar defects in wound healing are observed when SRP subunit imbalance is induced by over-expression of SRP68. Our studies support the existence of an RNA regulon containing Srp mRNAs that is controlled by CELF1. One implication is that altered function of CELF1 in myotonic dystrophy may contribute to changes in the extracellular matrix of affected muscle through defects in secretion.
authors.affiliation: Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, United States of America.
authors.forename: Joseph
authors.initials: J
authors.lastname: Russo
authors.affiliation: Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, United States of America.|Program in Cell and Molecular Biology, Colorado State University, Fort Collins, Colorado, United States of America.
authors.forename: Jerome E
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, United States of America.
authors.forename: Carolina M
authors.initials: CM
authors.lastname: López
authors.affiliation: Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Anderson
authors.affiliation: Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, United States of America.
authors.forename: Thuy-Mi P
authors.initials: TP
authors.lastname: Nguyen
authors.affiliation: Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, United States of America.|Program in Cell and Molecular Biology, Colorado State University, Fort Collins, Colorado, United States of America.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Heck
authors.affiliation: Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, United States of America.|Program in Cell and Molecular Biology, Colorado State University, Fort Collins, Colorado, United States of America.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Wilusz
authors.affiliation: Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, United States of America.|Program in Cell and Molecular Biology, Colorado State University, Fort Collins, Colorado, United States of America.
authors.forename: Carol J
authors.identifier: http://orcid.org/0000-0001-9939-0747
authors.initials: CJ
authors.lastname: Wilusz
mesh_terms: D000818:Animals; D000067879:CELF1 Protein / Q000235:genetics*; D051379:Mice; D032446:Myoblasts / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000378:metabolism; D020871:RNA Stability / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics*; D018271:Signal Recognition Particle / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D000067879:CELF1 Protein; C502743:CELF1 protein, mouse; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D018271:Signal Recognition Particle; D012313:RNA