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Identification of Novel Short C-Terminal Transcripts of Human SERPINA1 Gene

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 le...

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Autores principales: Matamala, Nerea, Aggarwal, Nupur, Iadarola, Paolo, Fumagalli, Marco, Gomez-Mariano, Gema, Lara, Beatriz, Martinez, Maria Teresa, Cuesta, Isabel, Stolk, Jan, Janciauskiene, Sabina, Martinez-Delgado, Beatriz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5249162/
https://www.ncbi.nlm.nih.gov/pubmed/28107454
http://dx.doi.org/10.1371/journal.pone.0170533
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author Matamala, Nerea
Aggarwal, Nupur
Iadarola, Paolo
Fumagalli, Marco
Gomez-Mariano, Gema
Lara, Beatriz
Martinez, Maria Teresa
Cuesta, Isabel
Stolk, Jan
Janciauskiene, Sabina
Martinez-Delgado, Beatriz
author_facet Matamala, Nerea
Aggarwal, Nupur
Iadarola, Paolo
Fumagalli, Marco
Gomez-Mariano, Gema
Lara, Beatriz
Martinez, Maria Teresa
Cuesta, Isabel
Stolk, Jan
Janciauskiene, Sabina
Martinez-Delgado, Beatriz
author_sort Matamala, Nerea
collection PubMed
description 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.
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spelling pubmed-52491622017-02-06 Identification of Novel Short C-Terminal Transcripts of Human SERPINA1 Gene Matamala, Nerea Aggarwal, Nupur Iadarola, Paolo Fumagalli, Marco Gomez-Mariano, Gema Lara, Beatriz Martinez, Maria Teresa Cuesta, Isabel Stolk, Jan Janciauskiene, Sabina Martinez-Delgado, Beatriz PLoS One Research Article 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. Public Library of Science 2017-01-20 /pmc/articles/PMC5249162/ /pubmed/28107454 http://dx.doi.org/10.1371/journal.pone.0170533 Text en © 2017 Matamala et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Matamala, Nerea
Aggarwal, Nupur
Iadarola, Paolo
Fumagalli, Marco
Gomez-Mariano, Gema
Lara, Beatriz
Martinez, Maria Teresa
Cuesta, Isabel
Stolk, Jan
Janciauskiene, Sabina
Martinez-Delgado, Beatriz
Identification of Novel Short C-Terminal Transcripts of Human SERPINA1 Gene
title Identification of Novel Short C-Terminal Transcripts of Human SERPINA1 Gene
title_full Identification of Novel Short C-Terminal Transcripts of Human SERPINA1 Gene
title_fullStr Identification of Novel Short C-Terminal Transcripts of Human SERPINA1 Gene
title_full_unstemmed Identification of Novel Short C-Terminal Transcripts of Human SERPINA1 Gene
title_short Identification of Novel Short C-Terminal Transcripts of Human SERPINA1 Gene
title_sort identification of novel short c-terminal transcripts of human serpina1 gene
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5249162/
https://www.ncbi.nlm.nih.gov/pubmed/28107454
http://dx.doi.org/10.1371/journal.pone.0170533
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