Here we introduce the collagen prolyl 4-hydroxylase alpha (I) subunit [C-P4H-alpha (I)] as a hypoxia sensitive gene, controlled at translational level. The collagen prolyl 4-hydroxylase plays a central role in collagen synthesis. The increased synthesis of the regulatory C-P4H-alpha subunit under long term hypoxia (36 h, 1% oxygen) in human HT1080 fibroblasts is controlled by an interaction of the RNA-binding protein nucleolin (~64 kDa form) at the 5'- and 3' untranslated regions (UTR) of the mRNA. The 5'UTR interaction of nucleolin depends on the existence of an AU- rich element, corresponding to UAAAUC or AAAUCU. At the 3'UTR, nucleolin assembles indirectly via protein/ protein interaction. The increased protein level of ~64 kDa nucleolin under hypoxia can be attributed to an autocatalytic cleavage of a high molecular weight nucleolin form. Thus, the alteration of translational efficiency by nucleolin is an important step in C- P4H-alpha (I) regulation under hypoxia.