title: Identification of Novel Short C-Terminal Transcripts of Human SERPINA1 Gene.
abstract: Human SERPINA1 gene is located on chromosome 14q31-32.3 and is organized into three (IA, IB, and IC) non-coding and four (II, III, IV, V) coding exons. This gene produces α1-antitrypsin (A1AT), a prototypical member of the serpin superfamily of proteins. We demonstrate that human peripheral blood leukocytes express not only a product corresponding to the transcript coding for the full-length A1AT protein but also two short transcripts (ST1C4 and ST1C5) of A1AT. In silico sequence analysis revealed that the last exon of the short transcripts contains an Open Reading Frame (ORF) and thus putatively can produce peptides. We found ST1C4 expression across different human tissues whereas ST1C5 was mainly restricted to leukocytes, specifically neutrophils. A high up-regulation (10-fold) of short transcripts was observed in isolated human blood neutrophils after activation with lipopolysaccharide. Parallel analyses by liquid chromatography-mass spectrometry identified peptides corresponding to C-terminal region of A1AT in supernatants of activated but not naïve neutrophils. Herein we report for the first time a tissue specific expression and regulation of short transcripts of SERPINA1 gene, and the presence of C-terminal peptides in supernatants from activated neutrophils, in vitro. This gives a novel insight into the studies on the transcription of SERPINA1 gene.
authors.affiliation: Molecular Genetics Unit, Instituto de Investigación de Enfermedades Raras (IIER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
authors.forename: Nerea
authors.initials: N
authors.lastname: Matamala
authors.affiliation: Department of Respiratory Medicine, Hannover Medical School, Hannover, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Hannover, Germany.
authors.forename: Nupur
authors.initials: N
authors.lastname: Aggarwal
authors.affiliation: Department of Biology and Biotechnologies, Biochemistry Unit, University of Pavia, Pavia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Iadarola
authors.affiliation: Department of Biology and Biotechnologies, Biochemistry Unit, University of Pavia, Pavia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Fumagalli
authors.affiliation: Molecular Genetics Unit, Instituto de Investigación de Enfermedades Raras (IIER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Gomez-Mariano
authors.affiliation: Respiratory Medicine Department, Coventry and Warwickshire University Hospital, Coventry, Warwickshire, United Kingdom.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Lara
authors.affiliation: Pneumology Department, Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Martinez
authors.affiliation: Bioinformatics Unit, Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Cuesta
authors.affiliation: Department of Pulmonology, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Stolk
authors.affiliation: Department of Respiratory Medicine, Hannover Medical School, Hannover, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Hannover, Germany.
authors.forename: Sabina
authors.initials: S
authors.lastname: Janciauskiene
authors.affiliation: Molecular Genetics Unit, Instituto de Investigación de Enfermedades Raras (IIER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
authors.forename: Beatriz
authors.identifier: http://orcid.org/0000-0001-6834-350X
authors.initials: B
authors.lastname: Martinez-Delgado
mesh_terms: D003198:Computer Simulation; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D016366:Open Reading Frames / Q000235:genetics; D016133:Polymerase Chain Reaction; D000515:alpha 1-Antitrypsin / Q000235:genetics*
chemical_list: D008070:Lipopolysaccharides; C043392:SERPINA1 protein, human; D000515:alpha 1-Antitrypsin