Host relieves lnc‐IRAK3‐3‐sequestered miR‐891b to attenuate apoptosis in Enterovirus 71 infection

Abstract

Enterovirus 71 (EV71) is an emerging life-threatening pathogen particularly in the Asia-Pacific region. Apoptosis is a major pathogenic feature in EV71 infection.However, which molecular mechanism participating in EV71-induced apoptosis is not completely understood. Long noncoding RNAs (lncRNAs), a newly discovered class of regulatory RNA molecules, govern a wide range of biological functions through multiple regulatory mechanisms. Whether lncRNAs involved in EV71-induced apoptosis was investigated in this study. We conducted an apoptosis-oriented approach by integrating lncRNA and mRNA profilings. lnc-IRAK3-3 is downregulated in EV71 infection and plays an important role in EV71 infection-induced apoptosis. Compensation of lnc-IRAK3-3 in EV71 infection promoted cell apoptosis wherein GADD45β expression was increased and further triggered caspase3 and PARP cleavage. Using bioinformatics analysis and functional assays, lnc-IRAK3-3 could functionally sequester miR-891b and GADD45β 3′UTR whereas miR-891b showed the inhibitory activity on GADD45β expression. Taken together, lnc-IRAK3-3 has the ability capturing miR-891b to enforce GADD45β expression and eventually promotes apoptosis. On the contrary, host cells suppress lnc-IRAK3-3 to relieve lnc-IRAK3-3sequestered miR-891b, restrain GADD45β, and attenuate apoptosis in EV71 infection that prevent host cells from severe damages. We discover a new molecular mechanism by which host cells counteract EV71-induced apoptosis through the lnc-IRAK3-3/miR-891b/GADD45β axis partially.

Integrated Analysis of mRNA and miRNA Changes in Two Haliotis diversicolor Genotypes and Their Hybrid

“…NEMs have been proven crucial regulators in hybrids' heterosis formation (Barber et al, 2012;Fang et al, 2013). Although research data of abalone miRNAs is quite limited, we could still classify the 71 NEMs into three functional categories according to the miRNA studies of other species: (1) Development, metabolism, and energy homeostasis: miR-196, miR-263, miR-9, miR-278, let-7i, and miR-33 (Reinhart et al, 2000;Hornstein et al, 2005;Aurelio and Stephen, 2006;Rayner et al, 2010;Nian et al, 2019;Zhou et al, 2020); (2) Immune response: miR-150, miR-1, miR-133, miR-4326, miR-152, miR-200, and miR-891 (Xiao et al, 2007;Xu et al, 2007Xu et al, , 2017Yang et al, 2007;Park et al, 2008;Tsuruta et al, 2011;Liao et al, 2019); and (3) Stress response and oxidation resistance: miR-2898, miR-885, and miR-466 (Aliaksandr et al, 2012;Alural et al, 2014;Deb and Sengar, 2020). The NEMs' functions also pattern with DY's vigorous phenotypes, highlighting the role of miRNA regulation in the abalone heterosis formation.…”

High throughput sequencing of whole transcriptome and construct of ceRNA regulatory network in RD cells infected with enterovirus D68

“…In 2019, Liao et al discovered that EV71 infection inhibited the endogenous expression of lnc-irak3-3, allowing miR-891b to be released from the chelation process of lnc-irak3-3. The proportional increase in miR-891b would further suppress the expression of mRNA GADD45β, resulting in a reduction in EV71-induced apoptosis [ 14 ]. Cheng et al discovered that EV-D68 could stimulate the accumulation of markers such as Ras GTPase activated protein binding protein 1 (G3BP1), T cell antigen 1 (TIA1), and human antigen R (HuR) in the early stages of infection, but prevented their accumulation later on.…”

Identification and analysis of long non-coding RNAs that are involved in inflammatory process in response to transmissible gastroenteritis virus infection

“…The lncRNAs play roles in regulating transcription, translation, and protein translocation [21][22][23][24][25]. LncRNAs can regulate translation by interacting with miRNA or act as precursors of miRNA [26][27][28].…”