Characterization of a COPD-Associated Functional Splicing Genetic Variant in Human Lung Tissue Long-Read Sequencing.

Background: Identification of COPD disease-causing genes is an important tool for understanding why COPD develops, who is at highest COPD risk, and how new COPD treatments can be developed. Previous COPD genetic studies have identified a highly significant genetic association near nephronectin ), a gene involved in tissue repair, but the biological mechanisms underlying this association are unknown.

Methods: Splicing quantitative trait locus analysis (sQTL) was performed to identify common genetic variants that alter RNA splicing in lung tissues.

A Cascade of Conformational Switches in SARS-CoV-2 Frameshifting: Coregulation by Upstream and Downstream Elements.

Targeting ribosomal frameshifting has emerged as a potential therapeutic intervention strategy against COVID-19. In this process, a -1 shift in the ribosomal reading frame encodes alternative viral proteins. Any interference with this process profoundly affects viral replication and propagation.

Structural determinants of inverted Alu-mediated backsplicing revealed by -MaP and -JuMP.

Biogenesis of circular RNA usually involves a backsplicing reaction where the downstream donor site is ligated to the upstream acceptor site by the spliceosome. For this reaction to occur, it is hypothesized that these sites must be in proximity. Inverted repeat sequences, such as Alu elements, in the upstream and downstream introns are predicted to base-pair and represent one mechanism for inducing proximity.

Abolished frameshifting for predicted structure-stabilizing SARS-CoV-2 mutants: implications to alternative conformations and their statistical structural analyses.

The SARS-CoV-2 frameshifting element (FSE) has been intensely studied and explored as a therapeutic target for coronavirus diseases, including COVID-19. Besides the intriguing virology, this small RNA is known to adopt many length-dependent conformations, as verified by multiple experimental and computational approaches. However, the role these alternative conformations play in the frameshifting mechanism and how to quantify this structural abundance has been an ongoing challenge.

Visualizing RNA structure ensembles by single-molecule correlated chemical probing.

RNA molecules fold to form complex internal structures. Many of these RNA structures populate ensembles with rheostat-like properties, with each state having a distinct function. Until recently, analysis of RNA structures, especially within cells, was limited to modeling either a single averaged structure or computationally-modeled ensembles.