RNA target specificity of the embryonic cell fate determinant POS-1

Farley, Brian M.; Pagano, John M.; Ryder, Seán

doi:10.1261/rna.1256708

Cited by 57 publications

(73 citation statements)

References 44 publications

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“…There are two MEX-3 binding sites in a conserved region of the glp-1 3Ј-UTR. The binding sites surround previously characterized binding sites for the RNAbinding proteins POS-1 and GLD-1 (28,29). The location of the binding sites suggests that regulation is direct and could potentially be inf luenced by the presence of other RNAbinding proteins.…”

Section: Fig 5 Validation Of the Mre Within The Regulatory Target Nmentioning

confidence: 70%

RNA recognition by the embryonic cell fate determinant and germline totipotency factor MEX-3

Pagano

Farley

Essien

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Totipotent stem cells have the potential to differentiate into every cell type. Renewal of totipotent stem cells in the germline and cellular differentiation during early embryogenesis rely upon posttranscriptional regulatory mechanisms. The Caenorhabditis elegans RNA binding protein, MEX-3, plays a key role in both processes. MEX-3 is a maternally-supplied factor that controls the RNA metabolism of transcripts encoding critical cell fate determinants. However, the nucleotide sequence specificity and requirements of MEX-3 mRNA recognition remain unclear. Only a few candidate regulatory targets have been identified, and the full extent of the network of MEX-3 targets is not known. Here, we define the consensus sequence required for MEX-3 RNA recognition and demonstrate that this element is required for MEX-3 dependent regulation of gene expression in live worms. Based on this work, we identify several candidate MEX-3 targets that help explain its dual role in regulating germline stem cell totipotency and embryonic cell fate specification.embryogenesis ͉ nematode ͉ RNA-binding protein ͉ post-transcriptional regulation ͉ maternal effect

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Section: Fig 5 Validation Of the Mre Within The Regulatory Target Nmentioning

confidence: 70%

RNA recognition by the embryonic cell fate determinant and germline totipotency factor MEX-3

Pagano

Farley

Essien

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…Region 4 and region 6 contain a predicted POS-1 and MEX-3 binding site, respectively (supplementary material Fig. S4) (Farley et al, 2008;Pagano et al, 2009). Consistent with multiple putative MEX-5 binding sites across the entire mom-2 3′UTR, no single region was found to be essential for MEX-5 binding ( Fig.…”

Section: Mex-3 Binds Ifet-1 An Eif4e-binding Proteinmentioning

confidence: 74%

“…In vivo functional characterization is often complicated by interdependent regulatory Regulation of maternal Wnt mRNA translation in C. elegans embryos relationships between these RBPs, as well as by the fact that many of them are required for correct blastomere fate specification. RNA binding analyses for several of these proteins have revealed a low sequence specificity for target RNAs, suggesting that specificity in vivo might be achieved by combinatorial binding of multiple proteins (Ryder et al, 2004;Pagano et al, 2007;Farley et al, 2008;Pagano et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Regulation of maternal Wnt mRNA translation inC. elegansembryos

et al. 2013

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The restricted spatiotemporal translation of maternal mRNAs, which is crucial for correct cell fate specification in early C. elegans embryos, is regulated primarily through the 3′UTR. Although genetic screens have identified many maternally expressed cell fatecontrolling RNA-binding proteins (RBPs), their in vivo targets and the mechanism(s) by which they regulate these targets are less clear. These RBPs are translated in oocytes and localize to one or a few blastomeres in a spatially and temporally dynamic fashion unique for each protein and each blastomere. Here, we characterize the translational regulation of maternally supplied mom-2 mRNA, which encodes a Wnt ligand essential for two separate cell-cell interactions in early embryos. A GFP reporter that includes only the mom-2 3′UTR is translationally repressed properly in oocytes and early embryos, and then correctly translated only in the known Wnt signaling cells. We show that the spatiotemporal translation pattern of this reporter is regulated combinatorially by a set of nine maternally supplied RBPs. These nine proteins all directly bind the mom-2 3′UTR in vitro and function as positive or negative regulators of mom-2 translation in vivo. The net translational readout for the mom-2 3′UTR reporter is determined by competitive binding between positive-and negativeacting RBPs for the 3′UTR, along with the distinct spatiotemporal localization patterns of these regulators. We propose that the 3′UTR of maternal mRNAs contains a combinatorial code that determines the topography of associated RBPs, integrating positive and negative translational inputs.

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“…Though both may be important for plant function, one of our aims was to identify potential recognition elements, which experiments suggest are between five and 20 nt long (Farley et al 2008;Hogan et al 2008;Pagano et al 2009). Motifs not belonging to any of the categories discussed above were scanned for regions of dense conservation (see Fig.…”

Section: Putative Recognition Elementsmentioning

confidence: 99%

Known and novel post-transcriptional regulatory sequences are conserved across plant families

Vaughn¹,

Ellingson²,

Mignone³

et al. 2012

RNA

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The sequence elements that mediate post-transcriptional gene regulation often reside in the 59 and 39 untranslated regions (UTRs) of mRNAs. Using six different families of dicotyledonous plants, we developed a comparative transcriptomics pipeline for the identification and annotation of deeply conserved regulatory sequences in the 59 and 39 UTRs. Our approach was robust to confounding effects of poor UTR alignability and rampant paralogy in plants. In the 39 UTR, motifs resembling PUMILIObinding sites form a prominent group of conserved motifs. Additionally, Expansins, one of the few plant mRNA families known to be localized to specific subcellular sites, possess a core conserved RCCCGC motif. In the 59 UTR, one major subset of motifs consists of purine-rich repeats. A distinct and substantial fraction possesses upstream AUG start codons. Half of the AUG containing motifs reveal hidden protein-coding potential in the 59 UTR, while the other half point to a peptideindependent function related to translation. Among the former, we added four novel peptides to the small catalog of conserved-peptide uORFs. Among the latter, our case studies document patterns of uORF evolution that include gain and loss of uORFs, switches in uORF reading frame, and switches in uORF length and position. In summary, nearly three hundred posttranscriptional elements show evidence of purifying selection across the eudicot branch of flowering plants, indicating a regulatory function spanning at least 70 million years. Some of these sequences have experimental precedent, but many are novel and encourage further exploration.

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RNA target specificity of the embryonic cell fate determinant POS-1

Cited by 57 publications

References 44 publications

RNA recognition by the embryonic cell fate determinant and germline totipotency factor MEX-3

RNA recognition by the embryonic cell fate determinant and germline totipotency factor MEX-3

Regulation of maternal Wnt mRNA translation inC. elegansembryos

Known and novel post-transcriptional regulatory sequences are conserved across plant families

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