SimiRa: A tool to identify coregulation between microRNAs and RNA-binding proteins

Abstract

Abbreviations: miRNA, microRNA; RBP, RNA-binding protein microRNAs and microRNA-independent RNA-binding proteins are 2 classes of post-transcriptional regulators that have been shown to cooperate in gene-expression regulation. We compared the genome-wide target sets of microRNAs and RBPs identified by recent CLIP-Seq technologies, finding that RBPs have distinct target sets and favor gene interaction network hubs. To identify microRNAs and RBPs with a similar functional context, we developed simiRa, a tool that compares enriched functional categories such as pathways and GO terms. We applied simiRa to the known functional cooperation between Pumilio family proteins and miR-221/222 in the regulation of tumor supressor gene p27 and show that the cooperation is reflected by similar enriched categories but not by target genes. SimiRa also predicts possible cooperation of microRNAs and RBPs beyond direct interaction on the target mRNA for the nuclear RBP TAF15. To further facilitate research into cooperation of microRNAs and RBPs, we made simiRa available as a web tool that displays the functional neighborhood and similarity of microRNAs and RBPs: http://vsicb-simira.helmholtz-muenchen.de.

PTRE-seq reveals mechanism and interactions of RNA binding proteins and miRNAs

“…Many RBP or miRNA binding sites have been shown to occur near predicted miRNA binding sites. In many cases these binding sites are immediately adjacent or even overlap 23 – 28 . Some RBPs cooperate with miRNAs in regulating the expression of specific genes.…”

Ancient and modern: hints of a core post‐transcriptional network driving chemotherapy resistance in ovarian cancer

“…The relationships that exist between RBPs and microRNAs, lncRNAs and other ncRNAs have yet to be fully characterized but this is becoming achievable using state‐of‐the‐art computational models like SimiRa (http://vsicb-simira.helmholtz-muenchen.de), CircInteractome (http://circinteractome.nia.nih.gov), doRiNA (http://dorina.mdc-berlin.de. ), and StarBase (http://starbase.sysu.edu.cn) that integrate and interrogate data from publically available RNA‐Seq and CLIP datasets to generate interaction maps and/or provide functional categorisations . The RBPs described below have been previously been characterized in the context of EOC and any known interactions with ncRNAs are outlined (Table ).…”

“…), and StarBase (starbase.sysu.edu.cn) that integrate and interrogate data from publically available RNA-Seq and CLIP datasets to generate interaction maps and/or provide functional categorisations. 65 The RBPs described below have been previously been characterized in the context of EOC and any known interactions with ncRNAs are outlined ( Table 1).…”

Guardian of Genetic Messenger-RNA-Binding Proteins

“…If RBPs are considered guardians of genetic messengers, then microRNAs may be referred to as “micro” guards of mRNAs. MicroRNAs control gene expression by the down regulating and fine tuning of transcripts by translational repression and/or degradation of respective mRNAs [ 12 , 13 , 14 ]. Regardless of the mechanism of miRNA operation, miRNAs hybridize to specific short sequences in the 3'-UTR of mRNAs [ 15 ].…”

“…Databases such as starBase ( ) have been developed to identify mRNA-miRNA (+ other non-coding RNAs) and mRNA-protein-RNA interaction networks [ 19 ]. Simultaneous binding of miRNA and RBPs to their respective sequences in the mRNA can be co-operative where both molecules work in harmony or antagonistically to oppose their respective functions [ 14 ].…”