Long non-coding RNAs coordinate cellular responses to stress

Abstract

Following the initial discovery of the heat shock RNA omega (hsrω) gene of Drosophila melanogaster to be non‐coding (nc) and also inducible by cell stress, other stress‐inducible long non‐coding RNAs (lncRNA) have been described in diverse organisms. In view of the rapid sequence divergence of lncRNAs, present knowledge of stress trasncriptome is limited and fragmented. Several known stress‐related lncRNAs, associated with specific nuclear speckled domains or nucleolus, provide structural base for sequestering diverse RNA‐processing/regulatory proteins. Others have roles in transcriptional or translational inhibition during stress or in signaling pathways; functions of several other lncRNAs are not yet known. Most stress‐related lncRNAs act primarily by modulating activity of the proteins to which they bind or by sequestering specific sets of proteins away from the active pool. A common emerging theme is that a given lncRNA targets one or more protein/s with key role/s in the cascade of events triggered by the stress and therefore has a widespread integrative effect. Since proteins associate with RNA through short sequence motifs, the overall base sequence of functionally similar ncRNAs is often not conserved except for specific motifs. The rapid evolvability of ncRNA sequences provides elegant modules for adaptability to changing environment as binding of one or the other protein to ncRNA can alter its structure and functions in distinct ways. Thus the stress‐related lncRNAs act as hubs in the cellular networks to coordinate activities of the members within and between different networks to maintain cellular homeostasis for survival or to trigger cell death. WIREs RNA 2012.