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. 2016 Jan 4;44(D1):D154-63.
doi: 10.1093/nar/gkv1308. Epub 2015 Dec 3.

RBP-Var: A Database of Functional Variants Involved in Regulation Mediated by RNA-binding Proteins

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Free PMC article

RBP-Var: A Database of Functional Variants Involved in Regulation Mediated by RNA-binding Proteins

Fengbiao Mao et al. Nucleic Acids Res. .
Free PMC article

Abstract

Transcription factors bind to the genome by forming specific contacts with the primary DNA sequence; however, RNA-binding proteins (RBPs) have greater scope to achieve binding specificity through the RNA secondary structure. It has been revealed that single nucleotide variants (SNVs) that alter RNA structure, also known as RiboSNitches, exhibit 3-fold greater local structure changes than replicates of the same DNA sequence, demonstrated by the fact that depletion of RiboSNitches could result in the alteration of specific RNA shapes at thousands of sites, including 3' UTRs, binding sites of microRNAs and RBPs. However, the network between SNVs and post-transcriptional regulation remains unclear. Here, we developed RBP-Var, a database freely available at http://www.rbp-var.biols.ac.cn/, which provides annotation of functional variants involved in post-transcriptional interaction and regulation. RBP-Var provides an easy-to-use web interface that allows users to rapidly find whether SNVs of interest can transform the secondary structure of RNA and identify RBPs whose binding may be subsequently disrupted. RBP-Var integrates DNA and RNA biology to understand how various genetic variants and post-transcriptional mechanisms cooperate to orchestrate gene expression. In summary, RBP-Var is useful in selecting candidate SNVs for further functional studies and exploring causal SNVs underlying human diseases.

Figures

Figure 1.
Figure 1.
Workflow to identify functional rbSNVs by RBP-Var.
Figure 2.
Figure 2.
Web-interface of RBP-Var. (AH) The snapshot of searching result for SNP rs1802295 in RBP-Var database.
Figure 3.
Figure 3.
The features of RBP-Var. (A) The component of rbSNVs derived from dbSNP. (B) Comparison of SNVs with category score 1/2 deposited in RBP-Var and RegulomeDB with damaging SNVs predicted by SIFT and PolyPhen2.(C) Comparison of RNA editing events with category score 1/2 deposited in RBP-Var with damaging RNA editing events predicted by SIFT and PolyPhen2.
Figure 4.
Figure 4.
Application of RBP-Var for an SNV related to type-2 diabetes. (A) The RBP binding signal for SNP rs1802295, which is a functional rbSNV associated with type 2 diabetes. The motif of binding by protein PABPC1L and PABPC3 are showed on the top of rs1802295. And the binding intensity around this SNP on mRNA of VPS26A by protein AGO2, PTBP1 from HeLa cell line, and IGF2BP3, WDR33, ELAVL1 from HEK293 cell line is illustrated in different tracks. The targeting site of miRNA hsa-miR-510 is marked by yellow vertical line. (B) The optimal secondary structure of RNA sequence from 200 bp of flanking regions on either side of SNP rs1802295 for wild-type of VPS26A and mutant of VPS26A induced by rs1802295. The green and red nucleotides represent the local sequence in interval of 50 bp for wild-type and mutant of VPS26A, respectively.

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