Program of the 2001 International Worm Meeting - Sternberg Lab ...

1099
1099. Characterization of translation
initiation factor eIF4E in C. elegans
development
Brett D. Keiper 1,3 , Anahita Amiri 2 ,
Eric J. Aamodt 1 , Susan Strome 2 ,
Robert E. Rhoads 1
1 Biochemistry and Molecular Biology, LSU
Health Sciences Center, Shreveport, LA 71130
2 Dept. of Biology, Indiana University,
Bloomington, IN 47405
3 email: bkeipe@lsuhsc.edu
Translational control of maternal and zygotic
mRNAs is a critical mode of gene regulation
during embryonic development. The control
generally involves regulated recruitment of
mRNAs to ribosomes. Recruitment begins with
the recognition of the mRNA 5’ cap by
translation initiation factor 4E (eIF4E). To
understand how translational control occurs
during development, we are studying the
regulation of eIF4E and mRNA cap recognition.
The majority of C. elegans mRNAs contain an
unusual trimethyl-guanosine (TMG) cap
structure as a result of trans-splicing in the
nucleus. The remaining mRNAs contain a
canonical monomethyl-guanosine (MMG)
cap. We have previously characterized five
eIF4E isoforms (IFE-1, -2, -3, -4, and -5)
expressed in C. elegans, which share 54-80%
amino acid sequence similarity [J. Biol. Chem.
275, 10590-10596 (2000)]. IFE-1, -2 and -5
bind to both TMG and MMG caps, while IFE-3
and IFE-4 recognize only MMG caps. This
suggests that IFE’s are involved in the
translation of both conventional and
trans-spliced mRNAs.
Three IFE’s (-1, -3 and -5) are enriched in the
adult gonad. IFE-1 is specifically associated
with the RNA-binding protein PGL-1 in P
granules during germline development.
Depletion of IFE-1 causes defects in
spermatogenesis but not oogenesis (see Amiri,
et al. abstract). Another germline-enriched
isoform, IFE-3, is most similar to human eIF4E
and is essential for embryonic viability in the
worm. Homozygous ife-3(ok191) embryos
arrest in early division stages of embryogenesis,
indicating that it performs a unique function
early in development. At least one of the
1099
TMG-binding isoforms is also required for
embryo viability, suggesting that one eIF4E of
each specificity is essential for translation of C.
elegans mRNAs. IFE-2 is found primarily in
somatic tissue. Given the differences in
cap-binding specificity, tissue-specific
expression and functional requirement, eIF4E
isoforms may provide a basis for translational
control mechanisms used in animal
development.