Cap-independent translation initiation of Apaf-1 mRNA based on a scanning mechanism is determined by some features of the secondary structure of its 5′ untranslated region

We have earlier shown that the 5'-untranslated region (5' UTR) of the mRNA coding for activation factor of apoptotic peptidase 1 (Apaf-1) can direct translation in vivo by strictly 5' end-dependent way even in the absence of m(7)G-cap. Dependence of translational efficiency on the cap availability for this mRNA turned out to be relatively low. In this study we demonstrate that this surprising phenomenon is determined the 5'-proximal part (domains I and II) of highly structured Apaf-1 5' UTR. Remarkably, domain II by itself was able to reduce dependence of the mRNA on the cap on its transferring to a short 5' UTR derived from a standard vector. We suggest that the low cap-dependence inherent to some cellular mRNAs may have an important physiological significance under those stress conditions when the function of cap-binding factor eIF4E is impaired.