DETECTION OF A SUB-SET OF POLYSOMAL MESSENGER-RNAS ASSOCIATED WITH MODULATION OF HYPUSINE FORMATION AT THE G1-S BOUNDARY - PROPOSAL OF A ROLE FOR EIF-5A IN ONSET OF DNA-REPLICATION

S phase entry, i.e. start of DNA replication, is a crucial step in pro liferation. Inhibition of S phase entry correlates with inhibition of hypusine formation, an event affecting only the eukaryotic initiation factor 5A (eIF-5A). Its hypusine-containing sequence was postulated to authorize polysomal utilization of specific transcripts for proteins necessary to enable DNA replication. Using mimosine to reversibly supp ress the hypusine-forming deoxyhypusyl hydroxylase (E.C. 1.14.99.29) i n cells while differentially displaying their polysomal versus non-pol ysomal mRNA populations, we report the detection and classification of several mRNA species that indeed disappear from and reappear at polys omes in concert with inhibition and disinhibition, respectively, of hy pusine formation. Based on initial sequence data, two translationally controlled enzymes, both critical for proliferation, are identified as candicate products of such mRNAs, methionine adenosyltransferase (E.C . 2.5.1.6) and cytochrome-c oxidase (EC 1.9.3.1) subunit I. The existe nce of such putative hypusine-dependent messenger nucleic acids (hymns ) provides the basis for a proposal on their molecular function in ons et of multiplication.