Coding and non coding RNAs

Introduction to RNA Complexity

  • Technological advances over the past decade have revealed the complexity of RNA interactions and functions.

  • Long non-coding RNAs (lncRNAs) can encode small peptides, blurring the lines between coding and non-coding RNA roles.

  • This review focuses on the dual roles of RNA and their implications for gene expression and evolution.

The Central Dogma of Molecular Biology

  • Central Dogma: Genetic information flows from DNA to RNA to protein, influencing cellular phenotype.

  • Traditional views limited RNA's role to just being an intermediate in protein synthesis.

  • High-throughput sequencing has uncovered extensive transcription in eukaryotic genomes, suggesting broad regulatory functions of RNA.

Coding vs Non-coding RNA

  • Only about 3% of eukaryotic genetic transcripts can encode proteins, leading to debates about the purpose of the remaining transcripts.

  • Projects like ENCODE indicate that over 80% of mammalian DNA is transcribed and many non-coding RNA (ncRNA) genes are active.

Long Non-Coding RNAs (lncRNAs)

  • Defined as transcripts longer than 200 nucleotides with low or no protein-coding potential.

  • lncRNAs can:

    • Regulate gene expression through epigenetic, transcriptional, post-transcriptional, and translational mechanisms.

    • Bind to other RNA molecules, acting as moderators or decoys in gene regulation.

    • Interact with proteins, influencing enzyme activity and localization.

Evidence for Coding Potential in lncRNAs

  • Recent analyses show many lncRNAs can associate with ribosomes and may contain small open reading frames (sORFs), indicating underestimated coding abilities.

  • Functional experiments have identified lncRNA-encoded micropeptides involved in biological processes.

  • Examples:

    • Steroid Receptor RNA Activator (SRA): Functions include roles in gene expression and can also encode a micropeptide that regulates its own transcriptional activities.

Circular RNAs (circRNAs)

  • Definition: Formed via backsplicing, connecting the 3' and 5' ends of exons.

  • CircRNAs can function as microRNA sponges, competitors during pre-mRNA splicing, and transcriptional regulators.

  • Some circRNAs, like circ-FBXW7 and circ-ZNF609, have been shown to code for proteins in biological contexts.

Techniques for Identifying sORFs in lncRNAs

  • Traditional methods struggle to predict lncRNA functions. Modern approaches like ribo-seq and mass spectrometry (MS) have emerged to help identify coding potential.

    • Ribo-seq: Can reveal the potential translation of sORFs by analyzing ribosome-protected RNA fragments.

    • Mass Spectrometry: Directly detects lncRNA-encoded peptides, providing evidence for coding potential.

Non-Coding Regulatory Functions Embedded in mRNAs

  • Recent discoveries indicate that mRNA's 3' untranslated regions (UTRs) have important regulatory functions beyond stability and location, influencing cancer progression.

  • Other non-coding roles include participation in RNA regulatory functions outside of protein coding, as seen with TP53 mRNA and its impact on tumor suppression.

Recent Perspectives on RNA Functionality

  • There is growing evidence supporting bifunctional RNAs, which may blur the lines between coding and non-coding classifications.

  • The roles of RNA in evolution and as potential sources for new protein coding genes are emphasized, suggesting that low-expressed non-coding RNAs may indeed contribute to new functionalities.

Conclusion

  • The complexity of RNA, including the capabilities of lncRNAs and circular RNAs, represents a significant area of research with implications for understanding gene expression and evolutionary biology.

  • Continued discovery of the regulatory roles of RNA will provide insights into fundamental biological processes.