ABSTRACT
TheBiP protein, a stress response protein, plays an important role in the
proper folding and assembly of nascent protein and in the scavenging of
misfolded proteins in the endoplasmic reticulum lumen. Translation of
BiP is directed by an internal ribosomal entry site (IRES) in the
5′ nontranslated region of the BiP mRNA. BiP IRES activity
increases when cells are heat stressed. Here we report that NSAP1
specifically enhances the IRES activity of BiP mRNA by interacting with
the IRES element. Overexpression of NSAP1 in 293T cells increased the
IRES activity of BiP mRNA, whereas knockdown of NSAP1 by small
interfering RNA (siRNA) reduced the IRES activity of BiP mRNA. The
amount of NSAP1 bound to the BiP IRES increased under heat stress
conditions, and the IRES activity of BiP mRNA was increased. Moreover,
the increase in BiP IRES activity with heat treatment was not observed
in cells lacking NSAP1 after siRNA treatment. BiP mRNAs were
redistributed from the heavy polysome to the light polysome in NSAP1
knockdown cells. Together, these data indicate that NSAP1 modulates
IRES-dependent translation of BiP mRNA through an RNA-protein
interaction under heat stress
conditions.