The broad application of next-generation sequencing technologies in conjunction with improved bioinformatics has helped to illuminate the complexity of the transcriptome, both in terms of quantity and variety. In humans, 70-90% of the genome is transcribed, but only ~2% carries the blueprint for proteins. Hence, there is a huge class of non-translated transcripts, called long non-coding RNAs (lncRNAs), which have received much attention in the past decade. Several studies have shown that lncRNAs are involved in a plethora of cellular signaling pathways and actively regulate gene expression via a broad selection of molecular mechanisms. Only recently, sequencing-based, transcriptome-wide studies have characterized different types of post-transcriptional chemical modifications of RNAs. These modifications have been shown to affect the fate of RNA and further expand the variety of the transcriptome. However, our understanding of their biological function, especially in the context of lncRNAs, is still in its infancy.
Researchers from Martin-Luther-University focus on three epitranscriptomic marks, namely pseudouridine (Ψ), N⁶-methyladenosine (m⁶A) and 5-methylcytosine (m⁵C) and introduce writers, readers, and erasers of these modifications. They present methods for their detection and provide insights into the distribution and function of these chemical modifications in selected, cancer-related lncRNAs.
Putative information flow impacting chemical RNA modifications
Internal and external signals lead to epitranscriptomic changes, which are applied by writer and eraser proteins, and subsequently conveyed by reader proteins. Some functions of these epitranscriptomic marks have already been shown while additional mechanisms can be envisioned.