title: Effects of airborne particulate matter on alternative pre-mRNA splicing in colon cancer cells.
abstract: Alternative pre-mRNA splicing plays key roles in determining tissue- and species-specific cell differentiation as well as in the onset of hereditary disease and cancer, being controlled by multiple post- and co-transcriptional regulatory mechanisms. We report here that airborne particulate matter, resulting from industrial pollution, inhibits expression and specifically affects alternative splicing at the 5' untranslated region of the mRNA encoding the bone morphogenetic protein BMP4 in human colon cells in culture. These effects are consistent with a previously reported role for BMP4 in preventing colon cancer development, suggesting that ingestion of particulate matter could contribute to the onset of colon cell proliferation. We also show that the underlying mechanism might involve changes in transcriptional elongation. This is the first study to demonstrate that particulate matter causes non-pleiotropic changes in alternative splicing.
authors: Laboratorio de Fisiología y Biología Molecular, Departamento de Fisiología, Biología Molecular y Celular, IFIBYNE-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, C1428EHA Buenos Aires, Argentina.
authors: Valeria
authors: V
authors: Buggiano
authors: Laboratorio de Fisiología y Biología Molecular, Departamento de Fisiología, Biología Molecular y Celular, IFIBYNE-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, C1428EHA Buenos Aires, Argentina.
authors: Ezequiel
authors: E
authors: Petrillo
authors: Laboratorio de Fisiología y Biología Molecular, Departamento de Fisiología, Biología Molecular y Celular, IFIBYNE-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, C1428EHA Buenos Aires, Argentina.
authors: Mariano
authors: M
authors: Alló
authors: Laboratorio de Fisiología y Biología Molecular, Departamento de Fisiología, Biología Molecular y Celular, IFIBYNE-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, C1428EHA Buenos Aires, Argentina.
authors: Celina
authors: C
authors: Lafaille
authors: Instituto de Ciencias Básicas y Medicina Experimental, Hospital Italiano de Buenos Aires, Argentina.
authors: María Ana
authors: MA
authors: Redal
authors: Department of Environmental Sciences, Faculty of Meteorology, Environment and Arid Land Agriculture, King Abdulaziz University, Jeddah, Saudi Arabia.
authors: Mansour A
authors: MA
authors: Alghamdi
authors: Department of Environmental Sciences, Faculty of Meteorology, Environment and Arid Land Agriculture, King Abdulaziz University, Jeddah, Saudi Arabia; Center of Excellence in Environmental Studies, King Abdulaziz University, Jeddah, Saudi Arabia.
authors: Mamdouh I
authors: MI
authors: Khoder
authors: Department of Environmental Sciences, Faculty of Meteorology, Environment and Arid Land Agriculture, King Abdulaziz University, Jeddah, Saudi Arabia.
authors: Magdy
authors: M
authors: Shamy
authors: Laboratorio de Fisiología y Biología Molecular, Departamento de Fisiología, Biología Molecular y Celular, IFIBYNE-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, C1428EHA Buenos Aires, Argentina. Electronic address: mmunoz@fbmc.fcen.uba.ar.
authors: Manuel J
authors: MJ
authors: Muñoz
authors: Laboratorio de Fisiología y Biología Molecular, Departamento de Fisiología, Biología Molecular y Celular, IFIBYNE-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, C1428EHA Buenos Aires, Argentina. Electronic address: ark@fbmc.fcen.uba.ar.
authors: Alberto R
authors: AR
authors: Kornblihtt
mesh_terms: D017398:Alternative Splicing / Q000187:drug effects*; D001483:Base Sequence; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology*; D017931:DNA Primers; D057809:HEK293 Cells; D006801:Humans; D052638:Particulate Matter / Q000494:pharmacology*; D012322:RNA Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D055415:Bone Morphogenetic Protein 4; D017931:DNA Primers; D052638:Particulate Matter; D012322:RNA Precursors; D012333:RNA, Messenger
keywords: Air pollution; Alternative splicing; Bone morphogenetic protein; Colon cancer cells; Particulate matter