SMS-seq

SMS-seq profiles RNA secondary and tertiary structure at single-molecule resolution by combining enzymatic or chemical probing with native RNA sequencing to capture non-amplified structural profiles and reveal structural heterogeneity.

Key Features:

• Single-molecule resolution: Enables interrogation of individual RNA molecules to reveal structural heterogeneity and intra-molecular dependencies.
• Comprehensive structural profiling: Employs enzymatic or chemical probing across numerous bases to map secondary structure throughout transcripts.
• Detection of tertiary interactions and dynamics: Captures tertiary interactions relevant to riboswitch ligand binding and complex three-dimensional RNA configurations, including mRNA features.
• Novel analysis methods: Applies mutual information–based analysis to detect dependencies and heterogeneity in single-molecule structural data.

Scientific Applications:

• Transcriptome-wide structural mapping: Produces per-molecule structural profiles for transcriptome-scale studies of RNA structure and function.
• Study of structural heterogeneity: Enables analysis of variation in secondary and tertiary structure across molecules within a population.
• Investigation of riboswitches and ligand interactions: Captures dynamics of riboswitch ligand binding and other ligand-dependent tertiary interactions.
• Exploration of mRNA structural features: Characterizes mRNA structural motifs implicated in post-transcriptional regulation.

Methodology:

Computational analysis of single-molecule native RNA sequencing and probing data using mutual information to interpret dependencies and structural heterogeneity.