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bioRxiv · 10.1101/2021.06.10.447916

Identifying proximal RNA interactions from cDNA-encoded crosslinks with ShapeJumper

Christy, T. W.·Giannetti, C. A.·Laederach, A.·Weeks, K. M.
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Abstract

SHAPE-JuMP is a concise strategy for identifying close-in-space interactions in RNA molecules. Nucleotides in close three-dimensional proximity are crosslinked with a bi-reactive reagent that covalently links the 2-hydroxyl groups of the ribose moieties. The identities of crosslinked nucleotides are determined using an engineered reverse transcriptase that jumps across crosslinked sites, resulting in a deletion in the cDNA that is detected using massively parallel sequencing. Here we introduce ShapeJumper, a bioinformatics pipeline to process SHAPE-JuMP sequencing data and to accurately identify through-space interactions. ShapeJumper identifies proximal interactions with near-nucleotide resolution using an alignment strategy that is optimized to tolerate the unique non-templated reverse-transcription profile of the engineered crosslink-traversing reverse-transcriptase. JuMP-inspired strategies are now poised to replace adapter-ligation for detecting RNA-RNA interactions in most crosslinking experiments.

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Christy, T. W., Giannetti, C. A., Laederach, A., Weeks, K. M.. 2021-06-11. Identifying proximal RNA interactions from cDNA-encoded crosslinks with ShapeJumper. https://doi.org/10.1101/2021.06.10.447916

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