Alternative splicing variants of proinsulin mRNA and the effects of excess proinsulin on cardiac morphogenesis

FEBS Lett. 2013 Jul 11;587(14):2272-7. doi: 10.1016/j.febslet.2013.05.060. Epub 2013 Jun 6.

Abstract

Alternative forms of proinsulin mRNA with differential translational capacities and unknown significance are expressed in several developing tissues and in the adult pancreas. In the chick embryo developing heart, we observed low expression of the translationally active transcript of embryonic proinsulin (Pro1B), and predominant expression of the intron 1-unspliced variant, translationally inactive. In the embryonic mouse heart, intron 1-unspliced isoform appeared after E12.5. This tight regulation is required for normal development, since overexpression of Pro1B resulted in abnormal cardiac morphogenesis in 40% of chick embryos, and was accompanied by changes in gene expression of Amhc1and Vmhc1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing*
  • Animals
  • Avian Proteins / genetics
  • Avian Proteins / metabolism
  • Cardiac Myosins / genetics
  • Cardiac Myosins / metabolism
  • Chick Embryo
  • Female
  • Gene Expression Regulation, Developmental
  • Heart / embryology*
  • Mice
  • Mice, Inbred C57BL
  • Morphogenesis*
  • Proinsulin / genetics*
  • Proinsulin / metabolism
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Receptor, Insulin / genetics
  • Receptor, Insulin / metabolism

Substances

  • Avian Proteins
  • Protein Isoforms
  • RNA, Messenger
  • Proinsulin
  • Receptor, Insulin
  • Cardiac Myosins