[talks] P Jiang preFPO

Melissa M. Lawson mml at CS.Princeton.EDU
Mon Feb 13 11:06:06 EST 2012

Peng Jiang will present his preFPO on Friday February 17 at Noon in 
Lewis Thomas Lab 118 (note location). The members of his committee 
are: Mona Singh, advisor; Hilary Coller (MOL) and Olga Troyanskaya, 
readers; Leonid Kruuglyak (Genomics) and Bernard Chazelle, nonreaders. 
Everyone is invited to attend his talk. His abstract follows below. 

----- Original Message -----

Computational Analysis of Transcriptional and post-Transcriptional regulation 

Transcription factors (TFs) and miRNAs are regulators for a wide range of biological processes. While binding specificities for numerous D. melanogaster TFs have been experimentally determined, the genomic binding targets for the majority of them are unknown, with even less known about the transcriptional regulators of miRNAs and the network-level interplay between TFs and miRNAs. We computationally constructed a large-scale transcriptional regulatory network for D. melanogaster. Based on several lines of experimental data, we annotated the transcription start sites for 37 integenic miRNAs. We uncovered conserved binding sites for TFs with known specificities in promoters of miRNAs and protein-coding genes. The inferred D. melanogaster transcriptional network is the largest to date, and consists of regulatory targets for 267 TFs, covering 56 intergenic miRNA loci and 11,232 protein-coding genes. Using this network, we predicted GO biological processes for miRNAs based upon their upstream regulators and downstream targets. Finally, we found that the network exhibits a surprisingly diverse array of network motifs consisting of both miRNAs and TFs. 

On the level of post-Transcriptional regulation, transcript degradation is a widespread and important mechanism for regulating protein abundance. Two major regulators of transcript degradation are RNA Binding Proteins (RBPs) and microRNAs (miRNAs). We computationally explored whether RBPs and miRNAs cooperate to promote transcript decay. We defined five RBP motifs based on the evolutionary conservation of their recognition sites in 3' UTRs as the binding motifs for Pumilio (PUM), U1A, Fox-1, Nova, and AU-rich element (ARE) binding proteins. Recognition sites for some of these RBPs tended to localize at the beginning or end of 3' UTRs. A specific group of miRNA recognition sites were enriched within 50 nts upstream and downstream of the RBP recognition sites of PUM, ARE, Fox-1 and U1A. The presence of both a PUM recognition site and a recognition site for preferentially co-occurring miRNAs was associated with faster decay of the associated transcripts. For PUM and its co-occurring miRNAs, binding of the RBP to its recognition sites was predicted to rescue nucleotides within nearby miRNA recognition sites from hybridization with other nucleotides at a higher rate than expected. miRNAs that preferentially co-occur with PUM binding sites tended to have recognition sites that are reverse complements to the PUM recognition motif. These sites have the potential to form hairpin secondary structures that would normally limit RISC accessibility, but would be more accessible to miRNAs in response to the binding of PUM. In sum, our computational analyses suggest that PUM can coordinately fine-tune the accessibility of multiple microRNA recognition sites. 

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