Mar 5, 2019

Discovery of Allele-Specific Protein-RNA Interactions in Human Transcriptomes

American Journal of Human Genetics
Emad Bahrami-Samani, Yi Xing

Abstract

Gene expression is tightly regulated at the post-transcriptional level through splicing, transport, translation, and decay. RNA-binding proteins (RBPs) play key roles in post-transcriptional gene regulation, and genetic variants that alter RBP-RNA interactions can affect gene products and functions. We developed a computational method ASPRIN (Allele-Specific Protein-RNA Interaction) that uses a joint analysis of CLIP-seq (cross-linking and immunoprecipitation followed by high-throughput sequencing) and RNA-seq data to identify genetic variants that alter RBP-RNA interactions by directly observing the allelic preference of RBP from CLIP-seq experiments as compared to RNA-seq. We used ASPRIN to systematically analyze CLIP-seq and RNA-seq data for 166 RBPs in two ENCODE (Encyclopedia of DNA Elements) cell lines. ASPRIN identified genetic variants that alter RBP-RNA interactions by modifying RBP binding motifs within RNA. Moreover, through an integrative ASPRIN analysis with population-scale RNA-seq data, we showed that ASPRIN can help reveal potential causal variants that affect alternative splicing via allele-specific protein-RNA interactions.

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Mentioned in this Paper

Genes
Sequence Determinations, RNA
Transcription, Genetic
Non-Aspirin
Protein Biosynthesis
Gene Expression
Encyclopedias
Binding (Molecular Function)
Protein Domain
RNA Splicing

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