Alternative splicing of human inducible nitric-oxide synthase mRNA. Tissue-specific regulation and induction by cytokines

N. Tony Eissa, Adam J. Strauss, Cynthia M. Haggerty, Esther Choo, Shan C. Chu, Joel Moss

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

Human inducible nitric-oxide synthase (iNOS) is responsible for nitric oxide synthesis in response to inflammatory mediators. The human iNOS gene, containing 26 exons, encodes a protein of 131 kDa. This study was aimed at investigating the presence of alternative splicing of human iNOS mRNA. Total RNA from human alveolar macrophages, nasal and bronchial epithelial cells, and several human tissues was transcribed to cDNA and analyzed using polymerase chain reaction with specific primers for segmental analysis of the iNOS gene. Four sites of alternative splicing were identified by sequence analysis; these included deletion of: (i) exon 5; (ii) exons 8 and 9; (iii) exons 9, 10, and 11; and (iv) exons 15 and 16. The deduced amino acid sequences of the novel iNOS cDNAs predict one truncated protein (resulting from exon 5 deletion) and three iNOS proteins with in-frame deletions. Southern analyses of polymerase chain reaction products were consistent with tissue-specific regulation of alternative splicing. In cultured cells, iNOS induction by cytokines and lipopolysaccharide was associated with an increase in alternatively spliced mRNA transcripts. Because iNOS is active as a dimer, the novel forms of alternatively spliced iNOS may be involved in regulation of nitric oxide synthesis.

Original languageEnglish (US)
Pages (from-to)27184-27187
Number of pages4
JournalJournal of Biological Chemistry
Volume271
Issue number43
DOIs
StatePublished - 1996
Externally publishedYes

Fingerprint

Alternative Splicing
Nitric Oxide Synthase Type II
Tissue
Cytokines
Messenger RNA
Exons
Polymerase chain reaction
Nitric Oxide
Complementary DNA
Genes
Polymerase Chain Reaction
Proteins
Alveolar Macrophages
Reaction products
Nose
Dimers
Sequence Analysis
Lipopolysaccharides
Amino Acid Sequence
Cultured Cells

ASJC Scopus subject areas

  • Biochemistry

Cite this

Alternative splicing of human inducible nitric-oxide synthase mRNA. Tissue-specific regulation and induction by cytokines. / Tony Eissa, N.; Strauss, Adam J.; Haggerty, Cynthia M.; Choo, Esther; Chu, Shan C.; Moss, Joel.

In: Journal of Biological Chemistry, Vol. 271, No. 43, 1996, p. 27184-27187.

Research output: Contribution to journalArticle

Tony Eissa, N. ; Strauss, Adam J. ; Haggerty, Cynthia M. ; Choo, Esther ; Chu, Shan C. ; Moss, Joel. / Alternative splicing of human inducible nitric-oxide synthase mRNA. Tissue-specific regulation and induction by cytokines. In: Journal of Biological Chemistry. 1996 ; Vol. 271, No. 43. pp. 27184-27187.
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