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

PLoS One. 2017 Jan 20;12(1):e0170533. doi: 10.1371/journal.pone.0170533. eCollection 2017.

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.

MeSH terms

  • Computer Simulation
  • Gene Expression Regulation / drug effects
  • Humans
  • In Vitro Techniques
  • Leukocytes / drug effects
  • Leukocytes / metabolism
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Lipopolysaccharides / pharmacology
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Open Reading Frames / genetics
  • Polymerase Chain Reaction
  • alpha 1-Antitrypsin / genetics*

Substances

  • Lipopolysaccharides
  • SERPINA1 protein, human
  • alpha 1-Antitrypsin

Grants and funding

This work has been partially funded by the Instituto de Salud Carlos III (www.isciii.es) grant PI14CIII/00070 (BMD) and SEPAR (Sociedad Española de Neumología y Cirugía Torácica, www.separ.es) grant 92/2014. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.