mRNA regulation in the "C. elegans" germ line

Scheckel, Claudia. mRNA regulation in the "C. elegans" germ line. 2011, Doctoral Thesis, University of Basel, Faculty of Science.


Official URL: http://edoc.unibas.ch/diss/DissB_9687

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The C. elegans germ line relies heavily on post-transcriptional regulation of gene expression but the scale of mRNA regulation in the germ line is still unknown. Germ cells initially divide mitotically, they then enter meiosis and finally differentiate into oocytes. Transcription ceases during oogenesis and does not get reactivated until the early embryo. The oocyte-to-embryo transition (OET) encompassing oocyte maturation, fertilization and early embryogenesis, therefore solely depends on maternal factors. Maternal mRNA storage describes the repression and stabilization of these factors until they are needed. At the four-cell stage, somatic blastomeres become dependent on zygotic transcription and at the same time a subgroup of maternal mRNAs (class II maternal mRNAs) gets specifically degraded. Many developmental decisions in the germ line are regulated by RNA binding proteins (RBPs). A crucial regulator is the STAR domain protein GLD-1, which is expressed in the central gonad. GLD-1 regulates many of the developmental decisions in the germ line and loss of GLD-1 prevents oogenesis and leads instead to the development of a proliferative tumor. GLD-1 binds a large number of mRNAs, and is known to repress the translation of various transcripts but the mechanism by which it does so is unknown.
We found that translation initiation of many germline mRNAs is repressed, and that GLD-1 globally represses translation initiation of its targets. Importantly, we revealed an additional role of GLD-1 in stabilizing a large number of its bound mRNAs, suggesting that GLD-1 plays a central role in maternal mRNA storage. While we could not detect an interaction between GLD-1 and translation initiation factors, we observed that GLD-1 associates with components of a conserved germline RNP complex. These components include the polyA binding protein (PABP), Y-box proteins, the Sm-like protein CAR-1 and the DDX6 helicase CGH-1, which has recently been implicated in maternal mRNA protection. Interestingly we found that while CGH-1 does not influence the translational repression of investigated GLD-1 targets, CGH-1 and GLD-1 stabilize a common set of transcripts. Remarkably, these co-regulated messages nearly exclusively encode for mRNAs that are required for the oocyte-to-embryo transition. We therefore propose a two-step model where GLD-1 binding prevents translation initiation and primes many targets for CGH-1-dependent mRNA stabilization, ultimately leading to mRNA storage.
Advisors:Gasser, Susan
Committee Members:Ephrussi, Anne and Ciosk, Rafal
Faculties and Departments:09 Associated Institutions > Friedrich Miescher Institut FMI
UniBasel Contributors:Gasser, Susan
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:9687
Thesis status:Complete
Number of Pages:135 S.
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edoc DOI:
Last Modified:22 Jan 2018 15:51
Deposited On:21 Dec 2011 15:32

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