Developmentally regulated muscle type-specific alternative splicing of the COOH-terminal variable region of fast skeletal muscle troponin T and an aberrant splicing pathway to encode a mutant COOH-terminus

Jian Ping Jin, Jennifer Wang, Ozgur Ogut

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Distinct from the cardiac and slow skeletal muscle troponin Ts, an alternative RNA splicing-generated COOH-terminal variable region exists in the fast skeletal muscle troponin T. Mutually exclusive splicing of exon 16 and 17 encoded sequence into the mature mRNA produces the α- and β-isoform, respectively. By cloning and sequence analysis of large numbers of fast troponin T cDNAs, we have quantitatively demonstrated that expression of the exon 16-encoded structure is mature fast muscle-specific (its utilization ranges from null in neonatal mouse muscles to 97% in adult chicken pectoralis), indicating a functional adaptation to the contractile feature of muscle. An aberrant splicing of this variable region to exclude both exons 16 and 17 from the mRNA was found in neonatal mouse skeletal muscle by cloning and sequencing characterization of a full length fTnT cDNA. The unusual splicing of exon 18 and exon 15 in the mRNA sequence results in not only a deletion of the exon 16/17 segment but also a shift of the downstream translation reading frame to produce a troponin T polypeptide with mutant COOH-terminus. Similar to an abnormal splicing of cardiac troponin T caused by cis-mutation and a dominant allele causing human familial hypertrophic cardiomyopathy, this trans-factor-determined aberrant mRNA splicing pathway generates a truncated troponin T molecule lacking the developmentally regulated fast muscle-specific COOH-terminal domain, indicating potential etiopathological significance.

Original languageEnglish (US)
Pages (from-to)540-544
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume242
Issue number3
DOIs
StatePublished - Jan 26 1998

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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