POSTAR2: deciphering the post-transcriptional regulatory logics

Abstract

Post-transcriptional regulation of RNAs is critical to the diverse range of cellular processes. The volume of functional genomic data focusing on post-transcriptional regulation logics continues to grow in recent years. In the current database version, POSTAR2 (http://lulab.life.tsinghua.edu.cn/postar), we included the following new features and data: updated ∼500 CLIP-seq datasets (∼1200 CLIP-seq datasets in total) from six species, including human, mouse, fly, worm, Arabidopsis and yeast; added a new module 'Translatome', which is derived from Ribo-seq datasets and contains ∼36 million open reading frames (ORFs) in the genomes from the six species; updated and unified post-transcriptional regulation and variation data. Finally, we improved web interfaces for searching and visualizing protein-RNA interactions with multi-layer information. Meanwhile, we also merged our CLIPdb database into POSTAR2. POSTAR2 will help researchers investigate the post-transcriptional regulatory logics coordinated by RNA-binding proteins and translational landscape of cellular RNAs.

Figure 1.

Framework to construct POSTAR2 database. (A) POSTAR2 covers six species including human, mouse, fly, worm, Arabidopsis and yeast. (B) POSTAR2 provides three modules: (i) ‘RBP’ module, which provides annotations and functions of RBPs, as well as RBP-binding sites; (ii) ‘RNA’ module, consisting of several sub-modules including ‘Binding sites’, ‘Crosstalk’, ‘Variation’ and ‘Disease’, which annotates the RBP-binding sites using various regulatory events and genomic variants; (iii) ‘Translatome’ module, which aims for exploring the translation landscape of genes across different tissues and cell lines. (C) POSTAR2 provides a user-friendly interface for searching and visualization such as table views, network views, histograms and heatmaps.

Figure 2.

Statistics of POSTAR2 database. (A) Number of RBPs in the human, mouse, worm, fly, Arabidopsis and yeast. (B) The distribution of human RBP-binding sites on chromosomes. HNRNPC, HNRNPA1 and U2AF2 have the largest number of binding sites among 171 human RBPs. (C) Genomic distribution of RBP-binding sites in six species identified using Piranha. (D) Summary of CLIP-seq and Ribo-seq datasets. (E) Diagram for different ORF categories. (i) Annotated ORFs (aORFs): ORFs that are annotated by reference annotation, which are colored with black in the diagram. (ii and iii) Truncated and extended ORFs: ORFs that contain the same stop codon with aORFs, but have different translation initiation sites. (iv) Internal ORFs: ORFs that are located in or have partial overlap with aORFs. (v and vi) Upstream and downstream ORFs: ORFs that are located upstream or downstream of aORFs. (vii) Unannotated ORFs: ORFs that are defined from transcripts without any reference annotation. (F) Number of ORFs for each category across six species.

Figure 3.

Integrative viewing of translation activity of a target gene (ADAM17) and its post-transcriptionally regulation events. (A) In the ‘Translatome’ module, all ORFs in ADAM17 are summarized based on their categories (i). Users can investigate each ORF by clicking on the name of the ORF (ii). For example, in ADAM17, estimation on the translation efficiency (iii) and the signal track (iv) reveals the potential of translation up-regulation in tumor samples compared to normal. (B) In the RBP module, search on ADAM17 provides the interactions network of ADAM17 gene and various RBPs (v). The number of RBPs binding along the transcript (vi) and genomic context of the binding sites (vii) can be visualized and searched. At last, the impact of SNVs in RBP-binding sites in both TCGA (viii) and COSMIC (ix) datasets further supports the association between ADAM17 and tumorigenesis.