G‐Quadruplexes act as sequence‐dependent protein chaperones

Abstract

Maintaining proteome health is important for cell survival. Nucleic acids possess the ability to prevent protein aggregation more efficiently than traditional chaperone proteins. In this study, we explore the sequence specificity of the chaperone activity of nucleic acids. Evaluating over 500 nucleic acid sequences' effects on protein aggregation, we show that the holdase chaperone effect of nucleic acids is sequence-dependent. G-Quadruplexes prevent protein aggregation via quadruplex:protein oligomerization. They also increase the folded protein level of a biosensor in E. coli. These observations contextualize recent reports of quadruplexes playing important roles in aggregation-related diseases, such as fragile X and amyotrophic lateral sclerosis (ALS), and provide evidence that nucleic acids have the ability to modulate the folding environment of E. coli.

5-amino levulinic acid inhibits SARS-CoV-2 infection in vitro

“…Among the molecular targets, a G-quadruplex (G4) structure is the potential target for its antiviral activity according to a recent report demonstrating that a G4-binding compound inhibited SARS-CoV-2 replication [ 18 , 19 ]. G4s are tetrahelical structures formed by guanine-rich regions of DNA or RNA, regulating genome stability, gene expression and protein quality control [ 20 , 21 ]. G4 structures are also found in the genome of many viruses including coronaviruses and can regulate viral replication cycles [ 22 , 23 ].…”

5-amino levulinic acid inhibits SARS-CoV-2 infection in vitro

“…Among the molecular targets, a Gquadruplex (G4) structure is the potential target for its antiviral activity according to a recent report demonstrating that a G4-binding compound inhibited SARS-CoV-2 replication [18,19]. G4s are tetrahelical structures formed by guanine-rich regions of DNA or RNA, regulating genome stability, gene expression and protein quality control [20,21]. G4 structures are also found in the genome of many viruses including coronaviruses and can regulate viral replication cycles [22,23].…”

Why are G-quadruplexes good at preventing protein aggregation?

“…To determine an individual sequence's G4r-value, an equation from (17) Protein expression, and Escherichia coli fluorescence assay Each pBAD33 backbone-based vector and pBAD/HisD-TagRFP675 were co-transformed into the E. coli strain MC4100(DE3) by heat shock. Expression of protein and RNA was performed following the previous study (3). Briefly, each transformant was grown on a LB plate containing 0.2% L-Arabinose, ampicillin (200 μg/ml), and chloramphenicol (50 μg/ml) at 42°C overnight.…”