Detection of a sub-set of polysomal mRNAs associated with modulation of hypusine formation at the G1-S boundary Proposal of a role for eIF-5A in onset of DNA replication

Document Type

Journal Article

Publication Date

6-12-1995

Journal

FEBS Letters

Volume

366

Issue

2-3

DOI

10.1016/0014-5793(95)00493-S

Keywords

Cell cycle control; eIF-5A; Hypusin; mRNA; Post-translational modification; Translational control

Abstract

S phase entry, i.e. start of DNA replication, is a crucial step in proliferation. Inhibition of S phase entry correlates with inhibition of hyposine formation, an event affecting only the eukaryotic initiation factor 5A (eIF-5A). Its hyposine-containing sequence was postulated to authorize polysomal utilization of specific transcripts for proteins necessary to enable DNA replication. Using mimosine to reversibly suppress the hypusine-forming deoxyhypusyl hydroxylase (E.C. 1.14.99.29) in cells while differentially displaying their polysomal versus non-polysomal mRNA populations, we report the detection and classification of several mRNA species that indeed disappear from and reappear at polysomes in concert with inhibition and disinhibition, respectively, of hypusine 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 existence of such putative hypusine-dependent messenger nucleic acids (kymns) provides the basis for a proposal on their molecular function in onset of multiplication. © 1995.

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