title: Modeling the combined effect of RNA-binding proteins and microRNAs in post-transcriptional regulation.
abstract: Recent studies show that RNA-binding proteins (RBPs) and microRNAs (miRNAs) function in coordination with each other to control post-transcriptional regulation (PTR). Despite this, the majority of research to date has focused on the regulatory effect of individual RBPs or miRNAs. Here, we mapped both RBP and miRNA binding sites on human 3'UTRs and utilized this collection to better understand PTR. We show that the transcripts that lack competition for HuR binding are destabilized more after HuR depletion. We also confirm this finding for PUM1(2) by measuring genome-wide expression changes following the knockdown of PUM1(2) in HEK293 cells. Next, to find potential cooperative interactions, we identified the pairs of factors whose sites co-localize more often than expected by random chance. Upon examining these results for PUM1(2), we found that transcripts where the sites of PUM1(2) and its interacting miRNA form a stem-loop are more stabilized upon PUM1(2) depletion. Finally, using dinucleotide frequency and counts of regulatory sites as features in a regression model, we achieved an AU-ROC of 0.86 in predicting mRNA half-life in BEAS-2B cells. Altogether, our results suggest that future studies of PTR must consider the combined effects of RBPs and miRNAs, as well as their interactions.
authors.affiliation: Graduate School of Informatics, Department of Health Informatics, Middle East Technical University, Üniversiteler Mahallesi, Dumlupınar Bulvarı, No:1, 06800 Ankara, Turkey.
authors.forename: Saber
authors.initials: S
authors.lastname: HafezQorani
authors.affiliation: Graduate School of Informatics, Department of Health Informatics, Middle East Technical University, Üniversiteler Mahallesi, Dumlupınar Bulvarı, No:1, 06800 Ankara, Turkey.
authors.forename: Atefeh
authors.initials: A
authors.lastname: Lafzi
authors.affiliation: Einthoven Laboratory of Experimental Vascular Medicine, Albinusdreef 2, 2333 ZA Leiden, The Netherlands Department of Nephrology, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
authors.forename: Ruben G
authors.initials: RG
authors.lastname: de Bruin
authors.affiliation: Einthoven Laboratory of Experimental Vascular Medicine, Albinusdreef 2, 2333 ZA Leiden, The Netherlands Department of Nephrology, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
authors.forename: Anton Jan
authors.initials: AJ
authors.lastname: van Zonneveld
authors.affiliation: Einthoven Laboratory of Experimental Vascular Medicine, Albinusdreef 2, 2333 ZA Leiden, The Netherlands Department of Nephrology, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
authors.forename: Eric P
authors.initials: EP
authors.lastname: van der Veer
authors.affiliation: Graduate School of Informatics, Department of Health Informatics, Middle East Technical University, Üniversiteler Mahallesi, Dumlupınar Bulvarı, No:1, 06800 Ankara, Turkey.
authors.forename: Yeşim Aydın
authors.initials: YA
authors.lastname: Son
authors.affiliation: Department of Computer Engineering, Antalya International University, Çıplaklı Mahallesi, Farabi Caddesi No:23, 07190 Döşemealtı, Antalya, Turkey hilal.kazan@antalya.edu.tr.
authors.forename: Hilal
authors.initials: H
authors.lastname: Kazan
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D002874:Chromosome Mapping; D019295:Computational Biology / Q000379:methods; D057809:HEK293 Cells; D006207:Half-Life; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics*; D009690:Nucleic Acid Conformation; D034622:RNA Interference; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; C471242:PUM1 protein, human; C471243:PUM2 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins
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