Evidences of a role for eukaryotic translation initiation factor 5A (eIF5A) in mouse embryogenesis and cell differentiation.
Eukaryotic translation initiation factor 5A (eIF5A) has a unique character: the presence of an unusual amino acid, hypusine, which is formed by post-translational modifications. Even before the identification of hypusination in eIF5A, the correlation between hypusine formation and protein synthesis, shifting cell proliferation rates, had already been observed. Embryogenesis is a complex process in which cellular proliferation and differentiation are intense. In spite of the fact that many studies have described possible functions for eIF5A, its precise role is under investigation, and to date nothing has been reported about its participation in embryonic development. In this study we show that eIF5A is expressed at all mouse embryonic post-implantation stages with increase in eIF5A mRNA and protein expression levels between embryonic days E10.5 and E13.5. Immunohistochemistry revealed the ubiquitous presence of eIF5A in embryonic tissues and organs at E13.5 day. Interestingly, stronger immunoreactivity to eIF5A was observed in the stomodeum, liver, ectoderm, heart, and eye, and the central nervous system; regions which are known to undergo active differentiation at this stage, suggesting a role of eIF5A in differentiation events. Expression analyses of MyoD, a myogenic transcription factor, revealed a significantly higher expression from day E12.5 on, both at the mRNA and the protein levels suggesting a possible correlation to eIF5A. Accordingly, we next evidenced that inhibiting eIF5A hypusination in mouse myoblast C2C12 cells impairs their differentiation into myotubes and decreases MyoD transcript levels. Those results point to a new functional role for eIF5A, relating it to embryogenesis, development, and cell differentiation.
Parreiras-e-Silva
Lucas T
LT
Faculty of Medicine at Ribeirão Preto, Department of Biochemistry and Immunology, University of São Paulo, Ribeirão Preto, SP, Brazil.
Luchessi
Augusto D
AD
Reis
Rosana I
RI
Oliver
Constance
C
Jamur
Maria C
MC
Ramos
Ricardo G P
RG
Oliveira
Eduardo B
EB
Curi
Rui
R
Costa-Neto
Claudio M
CM
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D047108:Embryonic Development / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000166:cytology; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology; D010448:Peptide Initiation Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000097574:Eukaryotic Translation Initiation Factor 5A
D017570:MyoD Protein; D010448:Peptide Initiation Factors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A; C057363:MyoD1 myogenic differentiation protein