Human insulin-like growth factor II leader 2 mediates internal initiation of translation

The Biochemical Journal
Susanne K PedersenFinn C Nielsen

Abstract

Insulin-like growth factor II (IGF-II) is a fetal growth factor, which belongs to the family of insulin-like peptides. During fetal life, the IGF-II gene generates three mRNAs with different 5' untranslated regions (UTRs), but identical coding regions and 3' UTRs. We have shown previously that IGF-II leader 3 mRNA translation is regulated by a rapamycin-sensitive pathway, whereas leader 4 mRNA is constitutively translated, but so far the significance of leader 2 mRNA has been unclear. Here, we show that leader 2 mRNA is translated efficiently in an eIF4E-independent manner. In a bicistronic vector system, the 411 nt leader 2 was capable of internal initiation via a phylogenetically conserved internal ribosome entry site (IRES), located in the 3' half of the leader. The IRES is composed of an approx. 120 nt ribosome recruitment element, followed by an 80 nt spacer region, which is scanned by the ribosomal pre-initiation complex. Since cap-dependent translation is down-regulated during cell division, leader 2 might facilitate a continuous IGF-II production in rapidly dividing cells during development.

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Citations

Jun 27, 2007·Nucleic Acids Research·Stephen D BairdMartin Holcik
Feb 14, 2012·Journal of Cell Science·Scott B FergusonTrudi Schüpbach
Sep 8, 2006·RNA·Stephen D BairdMartin Holcik
Jan 20, 2004·RNA·Catherine L JoplingAnne E Willis
Sep 21, 2013·International Journal of Molecular Sciences·Amaresh C PandaKotb Abdelmohsen
Jun 21, 2008·The FEBS Journal·Roberto I Vazquez-PadronAbdelouahab Aitouche
May 2, 2003·The Journal of Biological Chemistry·Donna M ValksAngela Clerk
Aug 23, 2005·Cancer Letters·Ivana GrbesaKoraljka Gall-Troselj

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