RNA editing regulates host immune response and T cell homeostasis in SARS-CoV-2 infection.

Adenosine to inosine (A-to-I) RNA editing by ADAR1 has been implicated in maintaining self-tolerance, preventing autoimmunity, and mediating antiviral immunity. Foreign viral double-stranded RNA triggers rapid interferon response and activates ADAR1 in the host immune system. Emerging data points to a role of ADAR1 A-to-I editing in the inflammatory response associated with severe COVID-19 disease. We identify A-to-I editing events within human whole transcriptome data from SARS-CoV-2 infected individuals, non-infected individuals, and individuals with other viral illnesses from nasopharyngeal swabs. High levels of RNA editing in host cells are associated with low SARS-CoV-2 viral load (p = 9.27 E-06), suggesting an inhibitory effect of ADAR1 on viral infection. Additionally, we find differentially expressed genes associated with RNA-modifications and interferon response. Single cell RNA-sequencing analysis of SARS-CoV-2 infected nasopharyngeal swabs reveals that cytotoxic CD8 T cells upregulate ADAR1 in COVID-19 positive samples (p = 0.0269). We further reveal ADAR1 expression increases with CD4 and CD8 T cell activation, and knockdown of ADAR1 leads to apoptosis and aberrant IL-2 secretion. Together, our data suggests A-to-I RNA editing is required to maintain healthy homeostasis of activated T cells to combat SARS-CoV-2 infection.

The Fragile X Protein Disordered Regions Bind a Novel RNA Target.

The fragile X proteins (FXPs) are a family of RNA-binding proteins that regulate mRNA translation to promote proper neural development and cognition in mammals. Of particular interest to researchers is the fragile X mental retardation protein (FMRP), as its absence leads to a neurodevelopmental disorder: fragile X syndrome (FXS), the leading monogenetic cause of autism spectrum disorders. A primary focus of research has been to determine mRNA targets of the FXPs in vivo through pull-down techniques, and to validate them through in vitro binding studies; another approach has been to perform in vitro selection experiments to identify RNA sequence and structural targets. These mRNA targets can be further investigated as potential targets for FXS therapeutics. The most established RNA structural target of this family of proteins is the G-quadruplex. In this article, we report a 99 nucleotide RNA target that is bound by all three FXPs with nanomolar equilibrium constants. Furthermore, we determined that the last 102 amino acids of FMRP, which includes the RGG motif, were necessary and sufficient to bind this RNA target. To the best of our knowledge, this is one of only a few examples of non-G-quadruplex, non-homopolymer RNAs bound by the RGG motif/C-termini of FMRP.

Preference Reversals Between Joint and Separate Evaluations With Multiple Alternatives and Context Effects.

Most research on preference reversal (PR) focuses on the evaluability hypothesis with one or two alternatives. However, people normally encounter more than two options in daily life. In this research, a third option was added to the PR effect choice sets in the traditional joint-separate evaluations mode to create a context effect. Three studies were conducted. Studies 1 and 2 showed that adding a third option to the choice sets changed the PR effect; either the attributes were both important or one was important and the other was not. Study 3 showed that the PR effect reappeared when a third option was added to the choice sets that had no PR effect with just two attributes that were difficult to evaluate independently in traditional evaluations modes. The three studies confirmed that preferences changed in multi-alternative evaluation modes, contradicting Hsee's (1996) work and showing that the context effect is stronger than that of the attribute's importance in the PR effect.

Burger or yogurt? Indulgent consumption in impression management contexts.

We conducted three studies to investigate indulgent choice in settings with and without impression management by public-private manipulation with evaluation. Study 1 showed that the participants were less indulgent under public scrutiny due to the employment of impression management. Study 2 focused on the impression management context to test the moderate effect of self-consciousness in two impression managed contexts. Study 3 focused on context without impression management to test the moderate effects of self-awareness on choices. We found that depending on differences in primed personality, individuals tended to make choices other than those they favoured privately when anticipating that others might form impressions of them based on the decisions made. The findings of all three studies support our basic prediction that people are less indulgent under impression management and suggest that people tend to manage their impression by eating healthier (less indulgently) in public.