Yehya, N. | Search bioRxiv

bioRxiv2022

Human red blood cells express the RNA sensor TLR7 and bind viral RNA

Red blood cells (RBCs) express the nucleic acid-sensing toll-like receptor 9 (TLR9) and bind CpG-containing DNA. However, whether human RBCs express other nucleic acid-sensing TLRs and bind RNA is unknown. Here we show that human RBCs express the RNA sensor, TLR7. TLR7 is present on the red cell membrane and associates with the RBC membrane protein Band 3. RBCs bind synthetic single-stranded RNA and RNA from pathogenic single-stranded RNA viruses. RNA acquisition by RBCs is attenuated by recombinant TLR7 and inhibitory oligonucleotides. Thus, RBCs may represent a previously unrecognized reservoir for RNA, although how RNA-binding by RBCs modulates the immune response has yet to be elucidated. These findings add to the growing list of non-gas exchanging RBC immune functions. SignificanceRed blood cells interact with pathogens, cytokines, and CpG-containing DNA; however, their immune functions remain largely unexplored. Here, we report that RBCs can bind synthetic or viral RNA and express TLR7. TLR7 interacts with the RBC membrane protein Band 3 and this interaction is increased during acute infection with SARS-CoV-2. Our study suggests that RBCs may have immune functions mediated by viral RNA, and RNA-carrying RBCs can potentially be a reservoir for RNA-based diagnostics.

immunology↗

bioRxiv2021

A spatial stochastic model reveals the role of supercoiling in transcription regulation

In Escherichia coli, translocation of RNA polymerase (RNAP) during transcription introduces supercoiling to DNA, which influences the initiation and elongation behaviors of RNAP. To quantify the role of supercoiling in transcription regulation, we develop a spatially resolved supercoiling model of transcription, describing RNAP-supercoiling interactions, topoisomerase activities, stochastic topological domain formation, and supercoiling diffusion in all transcription stages. This model establishes that transcription-induced supercoiling mediates the cooperation of co-transcribing RNAP molecules in highly expressed genes. It reveals that supercoiling transmits RNAP-accessible information through DNA and enables different RNAP molecules to communicate within and between genes. It thus predicts that a topological domain could serve as a transcription regulator, generating substantial transcription bursting and coordinating communications between adjacent genes in the domain. The model provides a quantitative platform for further theoretical and experimental investigations of how genome organization impacts transcription. Author SummaryDNA mechanics and transcription dynamics are intimately coupled. During transcription, the translocation of RNA polymerase overwinds the DNA ahead and underwinds the DNA behind, rendering the DNA supercoiled. The supercoiled DNA could, in return, influences the behavior of the RNA polymerase, and consequently the amount of mRNA product it makes. Furthermore, supercoils could propagate on the DNA over thousands of base pairs, impacting RNA polymerase molecules at faraway sites. These complicated interplays between supercoiling and RNA polymerase makes supercoiling an important transcription regulator. To quantitatively investigate the role of supercoiling in transcription, we build a spatially resolved model that links transcription with the generation, propagation, and dissipation of supercoiling. Our model reveals that supercoiling mediates transcription at multiple length scales. At a single-gene scale, we show that supercoiling gives rise to the collective motion of co-transcribing RNA polymerase molecules, supporting recent experimental observations. Additionally, large variations in mRNA production of a gene can arise from the constraints of supercoiling diffusion in a topological domain. At a multi-gene scale, we show that supercoiling dynamics allow two adjacent genes influence each others transcription kinetics, thus serving as a transcription regulator.

biophysics↗