The impact of ribosome association on lncRNA stability: a new layer of post-transcriptional control?

Long non-coding RNAs (lncRNAs) play crucial roles in cellular processes; however, the mechanisms controlling their stability are not well understood. Since the appropriate levels of lncRNAs in cells are required to carry out their functions, it is critical that their degradation is tightly controlled. Extensive research has shown that translation and degradation of messenger RNAs (mRNAs) are intricately linked, with repression of translation usually leading to degradation of the RNA. Recently, evidence has emerged to suggest that translation may also affect lncRNA stability. Ribosome engagement may stabilise lncRNAs by protecting them from nucleases or by promoting their degradation via ribosome-associated decay pathways such as nonsense-mediated decay. In this review, we first highlight specific human diseases that result from misregulation of lncRNA stability. We then explore the mechanisms underlying ribosome association and lncRNA stability, drawing comparisons with canonical mRNA mechanisms and highlighting emerging hypotheses that may be particularly relevant to lncRNAs. We also discuss how advanced techniques such as ribosome profiling can be applied to investigate whether lncRNAs are translated. Finally, we suggest future strategies to aid further understanding of lncRNA stability and its relationship with development and disease. Understanding the dynamic relationship between translation and lncRNA decay offers broad implications for RNA biology and provides new insights into the regulation of lncRNAs in both cellular and disease contexts.