Abstract
RNA regulation is essential to successful reproduction. Messenger RNAs delivered from parent to progeny govern early embryonic development. RNA-binding proteins (RBPs) are the key effectors of this process, regulating the translation and stability of parental transcripts to control cell fate specification events prior to zygotic gene activation. The KH-domain RBP MEX-3 is conserved from nematode to human. It was first discovered in Caenorhabditis elegans, where it is essential for anterior cell fate and embryo viability. Here, we show that loss of the endogenous mex-3 3´UTR disrupts its germline expression pattern. An allelic series of 3´UTR deletion variants identify repressing regions of the UTR and demonstrate that repression is not precisely coupled to reproductive success. We also show that several RBPs regulate mex-3 mRNA through its 3´UTR to define its unique germline spatiotemporal expression pattern. Additionally, we find that both poly(A) tail length control and the translation initiation factor IFE-3 contribute to its expression pattern. Together, our results establish the importance of the mex-3 3´UTR to reproductive health and its expression in the germline. Our results suggest that additional mechanisms control MEX-3 function when 3´UTR regulation is compromised.
Highlights
Regulation of mRNA metabolism occurs in all cells in all kingdoms of life
MEX-3 is a conserved RNA-binding protein found in most animals including humans
We define the importance of the 3 ́UTR in regulating MEX-3 expression pattern in vivo and characterize the RNA-binding proteins involved in this regulation
Summary
Regulation of mRNA metabolism occurs in all cells in all kingdoms of life. In the nucleus, premRNA undergoes splicing, 5 ́-capping, and 3 ́-end cleavage and polyadenylation [1]. MRNA is exported to the cytoplasm where it undergoes further post-transcriptional modifications prior to translation. MRNA can be stabilized by additional poly-adenylation or targeted for degradation by exonucleases through deadenylation and decapping [2,3]. This layer of regulation contributes to the amount of protein produced per transcript. Post-transcriptional regulation is especially critical in developmental processes such as gametogenesis and embryogenesis [4,5]. During the early stages of embryogenesis prior to the onset of zygotic transcription, inherited maternal mRNAs and proteins are essential to axis determination and cell fate specification [6,7,8]. Much remains to be learned about how they collaborate to achieve distinct spatiotemporal expression patterns for different maternal mRNAs
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