Improved simultaneous mapping of epigenetic features and 3D chromatin structure via ViCAR.

Methods to measure chromatin contacts at genomic regions bound by histone modifications or proteins are important tools to investigate chromatin organization. However, such methods do not capture the possible involvement of other epigenomic features such as G-quadruplex DNA secondary structures (G4s). To bridge this gap, we introduce ViCAR (viewpoint HiCAR), for the direct antibody-based capture of chromatin interactions at folded G4s.

G-quadruplex DNA structure is a positive regulator of transcription.

DNA structure can regulate genome function. Four-stranded DNA G-quadruplex (G4) structures have been implicated in transcriptional regulation; however, previous studies have not directly addressed the role of an individual G4 within its endogenous cellular context. Using CRISPR to genetically abrogate endogenous G4 structure folding, we directly interrogate the G4 found within the upstream regulatory region of the critical human oncogene.

MRT-ModSeq - Rapid Detection of RNA Modifications with MarathonRT.

Chemical modifications are essential regulatory elements that modulate the behavior and function of cellular RNAs. Despite recent advances in sequencing-based RNA modification mapping, methods combining accuracy and speed are still lacking. Here, we introduce MRT-ModSeq for rapid, simultaneous detection of multiple RNA modifications using MarathonRT.

MRT-ModSeq - Rapid detection of RNA modifications with MarathonRT.

Chemical modifications are essential regulatory elements that modulate the behavior and function of cellular RNAs. Despite recent advances in sequencing-based RNA modification mapping, methods combining accuracy and speed are still lacking. Here, we introduce MRT- ModSeq for rapid, simultaneous detection of multiple RNA modifications using MarathonRT.

RSCanner: rapid assessment and visualization of RNA structure content.

Motivation: The increasing availability of RNA structural information that spans many kilobases of transcript sequence imposes a need for tools that can rapidly screen, identify, and prioritize structural modules of interest.

Results: We describe RNA Structural Content Scanner (RSCanner), an automated tool that scans RNA transcripts for regions that contain high levels of secondary structure and then classifies each region for its relative propensity to adopt stable or dynamic structures. RSCanner then generates an intuitive heatmap enabling users to rapidly pinpoint regions likely to contain a high or low density of discrete RNA structures, thereby informing downstream functional or structural investigation.

Comprehensive in vivo secondary structure of the SARS-CoV-2 genome reveals novel regulatory motifs and mechanisms.

Severe-acute-respiratory-syndrome-related coronavirus 2 (SARS-CoV-2) is the positive-sense RNA virus that causes coronavirus disease 2019 (COVID-19). The genome of SARS-CoV-2 is unique among viral RNAs in its vast potential to form RNA structures, yet as much as 97% of its 30 kilobases have not been structurally explored. Here, we apply a novel long amplicon strategy to determine the secondary structure of the SARS-CoV-2 RNA genome at single-nucleotide resolution in infected cells.

The global and local distribution of RNA structure throughout the SARS-CoV-2 genome.

SARS-CoV-2 is the causative viral agent of COVID-19, the disease at the center of the current global pandemic. While knowledge of highly structured regions is integral for mechanistic insights into the viral infection cycle, very little is known about the location and folding stability of functional elements within the massive, ∼30kb SARS-CoV-2 RNA genome. In this study, we analyze the folding stability of this RNA genome relative to the structural landscape of other well-known viral RNAs.

Comprehensive in-vivo secondary structure of the SARS-CoV-2 genome reveals novel regulatory motifs and mechanisms.

SARS-CoV-2 is the positive-sense RNA virus that causes COVID-19, a disease that has triggered a major human health and economic crisis. The genome of SARS-CoV-2 is unique among viral RNAs in its vast potential to form stable RNA structures and yet, as much as 97% of its 30 kilobases have not been structurally explored in the context of a viral infection. Our limited knowledge of SARS-CoV-2 genomic architecture is a fundamental limitation to both our mechanistic understanding of coronavirus life cycle and the development of COVID-19 RNA-based therapeutics.