Are lncRNAs regulating host translation during infections?

Pathogenic bacteria produce powerful virulent factors, such as pore-forming toxins, that promote their survival and cause serious damage to the host. Host cells reply to membrane stresses and ionic imbalance by modifying gene expression at the epigenetic, transcriptional and translational level, to recover from the toxin attack. The fact that the majority of the human transcriptome encodes for non-coding RNAs (ncRNAs) raises the question: do host cells deploy non-coding transcripts to rapidly control the most energy-consuming process in cells-i.e., host translation-to counteract the infection? Here, researchers from the Institute of Biophysics at Trento discuss the intriguing possibility that membrane-damaging toxins induce, in the host, the expression of toxin-specific long non-coding RNAs (lncRNAs), which act as sponges for other molecules, encoding small peptides or binding target mRNAs to depress their translation efficiency. Unravelling the function of host-produced lncRNAs upon bacterial infection or membrane damage requires an improved understanding of host lncRNA expression patterns, their association with polysomes and their function during this stress. This field of investigation holds a unique opportunity to reveal unpredicted scenarios and novel approaches to counteract antibiotic-resistant infections.

Hypothesis of interplay between lncRNA expression changes and the
control of protein synthesis upon pore formation.

Upon pore formation, efflux of potassium ions and influx of calcium ions are well known to occur, due to the activity of a large variety of PFTs. A simplified connection between ion imbalance and the activation of three major pathways is depicted. These pathways control downstream target proteins, which are general factors of translation. Straight arrows connect processes related to the activation of pathways that control translation, proven to be involved in the response to ion imbalance triggered by pore-forming toxins or bacterial pathogens. In several cases, an association between lncRNA expression changes and regulation of these pathways has been demonstrated in cancer or viral infections. The cause and effect relationship of lncRNAs expression and the activation of pathways that control translation is at present not clear, as well as the mechanism of action behind such a connection. Therefore, we used dashed arrows to link lncRNA expression changes to pathways controlling translation, a connection that has been demonstrated for some lncRNAs but not with respect to bacterial infections, ion imbalance or pore formation by bacterial virulent factors.

Knap P, Tebaldi T, Di Leva F, Biagioli M, Dalla Serra M, Viero G. (2017) The Unexpected Tuners: Are LncRNAs Regulating Host Translation during Infections? Toxins (Basel) 9(11). [article]

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