: We have organized a """"""""3'UTRome Consortium"""""""" whose modENCODE goal is to map all 3' untranslated regions (3'UTRs) and their functional sequence elements in C. elegans. 3'UTRs are DNA encoded elements that are co-transcribed along with mRNAs and whose role is to regulate the activity of mRNA. We currently have only a partial and biased view of the global 3'UTRs sequences (3'UTRome) for any metazoan and have even less information on the motifs in the 3'UTRs that are used by trans-acting factors to drive gene regulation. Yet, what is known reveals a high level of complexity where 3'UTRs are often tissue-specific or are subject to alternative splicing events that lead to 3'UTR sequence diversity that parallels the diversity seen within the coding region of the transcript. Small non-coding RNAs (eg. microRNAs) are a class of posttranscriptional regulators that function through motifs found in the 3'UTRs; however only a subset of 3'UTR::microRNA motifs are though to be known. MicroRNAs add to the previously established fundamental role of RNA-binding proteins known to regulate expression; however, even less is known about these protein-binding motifs. C. elegans provides an excellent model to reveal the DNA-encoded functional elements that drive these complex events in a system where the genome is completely mapped and where 3'UTRs are comparatively compact. We propose to build on our preliminary studies and use a combination of in vitro, in vivo and in silico approaches to identify most or all 3'UTRs and functional sequence elements within them. Specifically, we propose to use genome-wide RT-PCR-based strategies to identify all 3'UTRs in C. elegans; to use computational approaches, microarray analysis and deep sequencing to reveal the vast majority of 3'UTR::microRNA binding motifs and use RIP-CHIP, Yeast-3-Hybrid and computational analysis to map the 3'UTR::RNA-binding-Protein motifs. ? ? To use genome data in medicine we need to build a map of the DNA elements that could affect every gene's activity. We are proposing to build a critical part of such a map using the model animal C. elegans by identifying all the 3'UTRs (sequence elements that regulate gene expression) as well as dissect the 3'UTRs and identify sub-elements that are responsible for the 3'UTR's functions. ? ? ? ?
| West, Sean M; Mecenas, Desirea; Gutwein, Michelle et al. (2018) Developmental dynamics of gene expression and alternative polyadenylation in the Caenorhabditis elegans germline. Genome Biol 19:8 |
| Weiser, Natasha E; Yang, Danny X; Feng, Suhua et al. (2017) MORC-1 Integrates Nuclear RNAi and Transgenerational Chromatin Architecture to Promote Germline Immortality. Dev Cell 41:408-423.e7 |
| Gan, Hin Hark; Gunsalus, Kristin C (2015) Assembly and analysis of eukaryotic Argonaute-RNA complexes in microRNA-target recognition. Nucleic Acids Res 43:9613-25 |
| Fernandez, Anita G; Mis, Emily K; Lai, Allison et al. (2014) Uncovering buffered pleiotropy: a genome-scale screen for mel-28 genetic interactors in Caenorhabditis elegans. G3 (Bethesda) 4:185-96 |
| Gan, Hin Hark; Gunsalus, Kristin C (2013) Tertiary structure-based analysis of microRNA-target interactions. RNA 19:539-51 |
| Fernandez, Anita G; Bargmann, Bastiaan O R; Mis, Emily K et al. (2012) High-throughput fluorescence-based isolation of live C. elegans larvae. Nat Protoc 7:1502-10 |
| Gunsalus, Kristin C; Rhrissorrakrai, Kahn (2011) Networks in Caenorhabditis elegans. Curr Opin Genet Dev 21:787-98 |
| Kiontke, Karin C; Felix, Marie-Anne; Ailion, Michael et al. (2011) A phylogeny and molecular barcodes for Caenorhabditis, with numerous new species from rotting fruits. BMC Evol Biol 11:339 |
| Mangone, Marco; Manoharan, Arun Prasad; Thierry-Mieg, Danielle et al. (2010) The landscape of C. elegans 3'UTRs. Science 329:432-5 |
| Fernandez, Anita G; Mis, Emily K; Bargmann, Bastiaan O R et al. (2010) Automated sorting of live C. elegans using laFACS. Nat Methods 7:417-8 |
Showing the most recent 10 out of 14 publications
