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.
S phase entry, i.e. start of DNA replication, is a crucial step in proliferation. 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 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 (hymns) provides the basis for a proposal on their molecular function in onset of multiplication.
Hanauske-Abel
H M
HM
Department of Pediatrics, Cornell University Medical College-The New York Hospital, NY 10031, USA.
Slowinska
B
B
Zagulska
S
S
Wilson
R C
RC
Staiano-Coico
L
L
Hanauske
A R
AR
McCaffrey
T
T
Szabo
P
P
D001483:Base Sequence; D002460:Cell Line; D004261:DNA Replication; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism*; D016193:G1 Phase; D006801:Humans; D008214:Lymphocytes; D008239:Lysine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D008716:Methionine Adenosyltransferase / Q000235:genetics / Q000378:metabolism*; D008898:Mimosine / Q000494:pharmacology; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors; D008969:Molecular Sequence Data; D010448:Peptide Initiation Factors / Q000502:physiology*; D011132:Polyribosomes / Q000737:chemistry*; D012333:RNA, Messenger / Q000235:genetics* / Q000302:isolation & purification; D016601:RNA-Binding Proteins; D016196:S Phase; D016415:Sequence Alignment; D000097574:Eukaryotic Translation Initiation Factor 5A
D003576:Electron Transport Complex IV; D008239:Lysine; D008716:Methionine Adenosyltransferase; D008898:Mimosine; D006899:Mixed Function Oxygenases; D010448:Peptide Initiation Factors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A; C100028:hypusine; C047991:deoxyhypusine hydroxylase