2-AIN-506, 2-AIN-252: Seminar in Bioinformatics (2), (4)
Summer 2024

Teshome Tilahun Bizuayehu, Kornel Labun, Martin Jakubec, Kirill Jefimov, Adnan Muhammad Niazi, Eivind Valen. Long-read single-molecule RNA structure sequencing using nanopore. Nucleic acids research, 50(20):e120. 2022.

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Download from publisher: https://doi.org/10.1093/nar/gkac775 PubMed

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RNA molecules can form secondary and tertiary structures that can regulate their 
localization and function. Using enzymatic or chemical probing together with 
high-throughput sequencing, secondary structure can be mapped across the entire 
transcriptome. However, a limiting factor is that only population averages can be 
obtained since each read is an independent measurement. Although long-read 
sequencing has recently been used to determine RNA structure, these methods still 
used aggregate signals across the strands to detect structure. Averaging across 
the population also means that only limited information about structural 
heterogeneity across molecules or dependencies within each molecule can be 
obtained. Here, we present Single-Molecule Structure sequencing (SMS-seq) that 
combines structural probing with native RNA sequencing to provide non-amplified, 
structural profiles of individual molecules with novel analysis methods. Our new 
approach using mutual information enabled single molecule structural 
interrogation. Each RNA is probed at numerous bases enabling the discovery of 
dependencies and heterogeneity of structural features. We also show that SMS-seq 
can capture tertiary interactions, dynamics of riboswitch ligand binding, and 
mRNA structural features.