Title
Computational assessment of the cooperativity between RNA binding proteins and MicroRNAs in Transcript Decay.
Abstract
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 39UTRs as the binding motifs for Pumilio (PUM), U1A, Fox-1, Nova, and UAUUUAU. Recognition sites for some of these RBPs tended to localize at the end of long 39UTRs. A specific group of miRNA recognition sites were enriched within 50 nts from the RBP recognition sites for PUM and UAUUUAU. 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 release nearby miRNA recognition sites from RNA secondary structures. The mammalian miRNAs that preferentially co-occur with PUM binding sites have recognition seeds that are reverse complements to the PUM recognition motif. Their binding sites have the potential to form hairpin secondary structures with proximal PUM binding sites 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 a specific set of RBPs and miRNAs work together to affect transcript decay, with the rescue of miRNA recognition sites via RBP binding as one possible mechanism of cooperativity.
Year
DOI
Venue
2013
10.1371/journal.pcbi.1003075
PLOS COMPUTATIONAL BIOLOGY
Keywords
Field
DocType
computational biology,rna binding proteins,micrornas
Sequence alignment,Cooperativity,RNA,Conserved sequence,Binding site,Biology,microRNA,Messenger RNA,RNA-binding protein,Bioinformatics,Genetics
Journal
Volume
Issue
ISSN
9
5
1553-7358
Citations 
PageRank 
References 
2
0.39
1
Authors
3
Name
Order
Citations
PageRank
Peng Jiang120.39
Mona Singh235722.75
Hilary A Coller3722.97