title: LMKB/MARF1 localizes to mRNA processing bodies, interacts with Ge-1, and regulates IFI44L gene expression.
abstract: The mRNA processing body (P-body) is a cellular structure that regulates the stability of cytoplasmic mRNA. MARF1 is a murine oocyte RNA-binding protein that is associated with maintenance of mRNA homeostasis and genomic stability. In this study, autoantibodies were used to identify Limkain B (LMKB), the human orthologue of MARF1, as a P-body component. Indirect immunofluorescence demonstrated that Ge-1 (a central component of the mammalian core-decapping complex) co-localized with LMKB in P-bodies. Two-hybrid and co-immunoprecipitation assays were used to demonstrate interaction between Ge-1 and LMKB. The C-terminal 120 amino acids of LMKB mediated interaction with Ge-1 and the N-terminal 1094 amino acids of Ge-1 were required for interaction with LMKB. LMKB is the first protein identified to date that interacts with this portion of Ge-1. LMKB was expressed in human B and T lymphocyte cell lines; depletion of LMKB increased expression of IFI44L, a gene that has been implicated in the cellular response to Type I interferons. The interaction between LMKB/MARF1, a protein that contains RNA-binding domains, and Ge-1, which interacts with core-decapping proteins, suggests that LMKB has a role in the regulation of mRNA stability. LMKB appears to have different functions in different cell types: maintenance of genomic stability in developing oocytes and possible dampening of the inflammatory response in B and T cells.
authors.affiliation: Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America; Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Donald B
authors.initials: DB
authors.lastname: Bloch
authors.affiliation: Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Pingcheng
authors.initials: P
authors.lastname: Li
authors.affiliation: Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Emily G
authors.initials: EG
authors.lastname: Bloch
authors.affiliation: Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Berenson
authors.affiliation: Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Rita L
authors.initials: RL
authors.lastname: Galdos
authors.affiliation: Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America; Cardiovascular Research Center, Cardiology Division of the Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Arora
authors.affiliation: Cardiovascular Research Center, Cardiology Division of the Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Malhotra
authors.affiliation: Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Connie
authors.initials: C
authors.lastname: Wu
authors.affiliation: Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Weihong
authors.initials: W
authors.lastname: Yang
mesh_terms: D000818:Animals; D000941:Antigens / Q000235:genetics* / Q000378:metabolism; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002460:Cell Line; D022083:Cytoplasmic Structures / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D004722:Endoribonucleases; D005455:Fluorescent Antibody Technique; D055785:Gene Knockdown Techniques; D006801:Humans; D047468:Immunoprecipitation; D011485:Protein Binding; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques
chemical_list: D000941:Antigens; D001323:Autoantibodies; D001324:Autoantigens; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C507914:EDC4 protein, human; C065888:IFI44 protein, human; D011506:Proteins; D012333:RNA, Messenger; D004722:Endoribonucleases; C000631945:MARF1 protein, human
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