Differential analysis of RNA structure probing experiments at nucleotide resolution: uncovering regulatory functions of RNA structure.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
22 07 2022
22 07 2022
Historique:
received:
14
08
2021
accepted:
05
07
2022
entrez:
22
7
2022
pubmed:
23
7
2022
medline:
27
7
2022
Statut:
epublish
Résumé
RNAs perform their function by forming specific structures, which can change across cellular conditions. Structure probing experiments combined with next generation sequencing technology have enabled transcriptome-wide analysis of RNA secondary structure in various cellular conditions. Differential analysis of structure probing data in different conditions can reveal the RNA structurally variable regions (SVRs), which is important for understanding RNA functions. Here, we propose DiffScan, a computational framework for normalization and differential analysis of structure probing data in high resolution. DiffScan preprocesses structure probing datasets to remove systematic bias, and then scans the transcripts to identify SVRs and adaptively determines their lengths and locations. The proposed approach is compatible with most structure probing platforms (e.g., icSHAPE, DMS-seq). When evaluated with simulated and benchmark datasets, DiffScan identifies structurally variable regions at nucleotide resolution, with substantial improvement in accuracy compared with existing SVR detection methods. Moreover, the improvement is robust when tested in multiple structure probing platforms. Application of DiffScan in a dataset of multi-subcellular RNA structurome and a subsequent motif enrichment analysis suggest potential links of RNA structural variation and mRNA abundance, possibly mediated by RNA binding proteins such as the serine/arginine rich splicing factors. This work provides an effective tool for differential analysis of RNA secondary structure, reinforcing the power of structure probing experiments in deciphering the dynamic RNA structurome.
Identifiants
pubmed: 35869080
doi: 10.1038/s41467-022-31875-3
pii: 10.1038/s41467-022-31875-3
pmc: PMC9307511
doi:
Substances chimiques
Nucleotides
0
RNA Probes
0
RNA
63231-63-0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4227Informations de copyright
© 2022. The Author(s).
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