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Role of C. elegans eIF4E-binding protein, IFET-1 in post-transcriptional gene regulation
thesisposted on 24.02.2017, 01:38 by Sengupta, Madhu Sharma
4E-BP family proteins play important role in translational control of all cellular processes. One of the most conserved 4E-BP is the 4E-Transporter family (4E-T). The C. elegans homolog of 4E-T, IFET-1 (ife-transporter) has previously been identified as germline enriched, however little is known about its function in early germ cell development. We found that in the absence of IFET-1, the adult gonad was masculinized and displayed additional gross morphological defects. IFET-1 is also required for translational repression of several maternal mRNAs, and this process involved other broad-scale translational regulators. We determined that IFET-1 localized to P-granules throughout the gonad and in the germ cell lineage in embryos and was required for normal P-granule integrity. In addition to this, IFET-1 was required for localization of some conserved P-granule components in the gonad. One of the conserved domains of 4E-Ts is the C-terminal Q-rich domain. Through analysis of transgenic worm expression, we found that the Q-domain was important for perinuclear P-granule localization of IFET-1. We characterized IFET-1 interacting proteins by using immuno-precipitation combined with mass spectrometry and identified small number of proteins that interact with IFET-1. Interestingly, we identified only one of the five eIF4E family member, IFE-3, strongly associated with IFET-1. We propose that IFET-1/IFE-3 interaction is required for translational repression of mono-methylated capped mRNAs in the germline. Taken together, the study provides valuable insight in the translational regulation mechanism in C. elegans germline context.