D104–D114 Nucleic Acids Research, 2017, Vol. 45, Database issue Published online 5 October 2016 doi: 10.1093/nar/gkw888 POSTAR: a platform for exploring post-transcriptional regulation coordinated by RNA-binding proteins Boqin Hu1,†, Yu-Cheng T. Yang1,2,†, Yiming Huang1, Yumin Zhu1 and Zhi John Lu1,*
1MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Center for Plant Biology and Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China and 2Department of Statistics, University of California Los Angeles, Los Angeles, CA 90095-1554, USA
Received July 08, 2016; Revised September 23, 2016; Accepted September 27, 2016
ABSTRACT post-transcriptional regulation not fully explored and con- nected with existing knowledge. Although RNA splicing We present POSTAR (http://POSTAR.ncrnalab.org), a has been well-studied, other post-regulatory signatures, resource of POST-trAnscriptional Regulation coordi- such as RNA modification and RNA editing, have not been nated by RNA-binding proteins (RBPs). Precise char- profiled until recently3–5 ( ). Furthermore, most studies of acterization of post-transcriptional regulatory maps genomic variants (e.g. GWAS SNPs (6) and cancer somatic has accelerated dramatically in the past few years. mutations (7)) have mainly focused on the transcriptional Based on new studies and resources, POSTAR sup- level (8,9). Recently, there has been increasing interest in plies the largest collection of experimentally probed studying the association between post-transcriptional reg- (∼23 million) and computationally predicted (approx- ulation and disease-associated variation (10). In addition, imately 117 million) RBP binding sites in the human post-transcriptional regulation could regulate cell differen- and mouse transcriptomes. POSTAR annotates ev- tiation (11) and influence the scope of the druggable pro- teome (12). However, post-transcriptional interactions be- ery transcript and its RBP binding sites using exten- tween cell state-associated genes and druggable genes and sive information regarding various molecular regula- their impacts on cell differentiation, pathology and clinical tory events (e.g., splicing, editing, and modification), treatment remain largely uncharacterized. To perform such RNA secondary structures, disease-associated vari- studies, researchers require a platform that facilitates inte- ants, and gene expression and function. Moreover, gration and association of multi-layer information to illumi- POSTAR provides a friendly, multi-mode, integrated nate the mechanisms underlying post-transcriptional regu- search interface, which helps users to connect mul- lation. tiple RBP binding sites with post-transcriptional reg- RNA transcripts do not function as naked RNAs in eu- ulatory events, phenotypes, and diseases. Based on karyotic cells from birth to death; instead, they are dy- our platform, we were able to obtain novel insights namically bound by various post-transcriptional regula- into post-transcriptional regulation, such as the puta- tory factors, including RNA-binding proteins (RBPs) and microRNAs (miRNAs) (13,14). Recently developed high- tive association between CPSF6 binding, RNA struc- throughput assays (e.g. CLIP-seq and RNAcompete tech- tural domains, and Li-Fraumeni syndrome SNPs. In nologies), together with computational tools, enabled re- summary, POSTAR represents an early effort to sys- searchers to obtain transcriptome-wide binding maps of tematically annotate post-transcriptional regulatory RBPs and miRNAs at high resolution (15,16). Most RNA maps and explore the putative roles of RBPs in hu- processing reactions (e.g. alternative splicing, alternative man diseases. polyadenylation and nucleotide modification) and regula- tory events (e.g. subcellular localization, RNA stability and translation efficiency) are mediated by miRNAs and RBPs. INTRODUCTION Constructing accurate and comprehensive RBP-RNA and The regulatory maps of genomes have been revealed miRNA-RNA interaction maps at high resolution is a nec- by various high-throughput sequencing assays from in- essary step toward interpreting their mechanistic roles in dividual groups and consortium efforts such as the EN- post-transcriptional regulation. CODE project (1) and Roadmap Epigenomics project (2). Although there are several databases for CLIP-seq- Most previous studies have focused on cis-regulation, the derived RBP binding sites, such as CLIPZ (17), starBase epigenome, the transcriptome, and the proteome, leaving (18), DoRiNA (19) and CLIPdb (20), they merely provide
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