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Role of C. elegans eIF4E-binding protein, IFET-1 in post-transcriptional gene regulation

thesis
posted 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.

History

Principal supervisor

Peter Boag

Year of Award

2016

Department, School or Centre

Biochemistry and Molecular Biology

Campus location

Australia

Course

Doctor of Philosophy

Degree Type

DOCTORATE

Faculty

Faculty of Medicine Nursing and Health Sciences

Exports