Sequence- and structure-specific RNA oligonucleotide binding attenuates heterogeneous nuclear ribonucleoprotein A1 dysfunction

• DOI: 10.3389/fmolb.2023.1178439
• Publication Date: 2023-06-24T08:48:39Z
• Authors: Joseph P. Clarke; Patricia A. Thibault; Sakina Fatima; Hannah E. Salapa; Subha Kalyaanamoo...; Aravindhan Ganesan; Michael C. Levin
• Keywords: Stress granule

The RNA binding protein heterogeneous nuclear ribonucleoprotein A1 (A1) regulates metabolism, which is crucial to maintaining cellular homeostasis. dysfunction mechanistically contributes reduced cell viability and loss, but molecular mechanisms of how affects methodologies attenuate its dysfunction, are lacking. Utilizing in silico modeling an vitro optogenetic system, this study examined the consequences oligonucleotide (RNAO) treatment on attenuating downstream effects. In thermal shift experiments revealed that RNAOs Recognition Motif 1 stabilized by sequence- structure-specific RNAO-A1 interactions. Using optogenetics model we show significantly attenuated abnormal cytoplasmic self-association kinetics clustering. Downstream demonstrate clustering formation stress granules, activates stress, inhibits translation. With RNAO treatment, granule attenuated, inhibited, translation restored. This provides evidence attenuates effects, thus allowing for development A1-specific therapies restore