- Ribonuclease R (RNase R) is a 3′ to 5′ exoribonuclease that plays a crucial role in RNA metabolism, particularly in the degradation of structured RNA molecules. Belonging to the RNase II/R family, RNase R is distinct from many other exoribonucleases due to its remarkable ability to degrade highly structured RNAs without requiring additional helicase activity or ATP. This makes it an essential enzyme for RNA surveillance and quality control in both prokaryotic and eukaryotic cells.
- Structurally, RNase R contains a conserved RNase II-like catalytic domain responsible for exonucleolytic activity, along with RNA-binding motifs such as the S1 and KH domains. These domains help the enzyme recognize and bind to various RNA substrates. RNase R performs processive degradation, meaning it can continuously cleave nucleotides from the 3′ end of RNA without dissociating. Its ability to unwind and digest double-stranded or structured regions—such as stem-loops or hairpins—sets it apart from enzymes like RNase II, which typically stall at such secondary structures.
- Biologically, RNase R is integral to RNA quality control pathways. In bacteria like Escherichia coli, RNase R is involved in the degradation of defective ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), and messenger RNAs (mRNAs), particularly those with extensive secondary structure that resist degradation by other exonucleases. Its expression and stability are often upregulated under stress conditions, such as cold shock or nutrient depletion, to facilitate the recycling of RNA molecules and conserve cellular energy.
- In eukaryotic systems, RNase R or its homologs participate in similar processes, such as the elimination of faulty RNAs, degradation of non-coding RNA intermediates, and maintenance of RNA homeostasis. RNase R is also involved in ribosome maturation by trimming precursor rRNAs during ribosome biogenesis.
- In molecular biology research, RNase R has become a valuable tool for enriching circular RNAs (circRNAs). Because circRNAs lack free 3′ and 5′ ends, they are resistant to RNase R digestion, while most linear RNAs are degraded. This property allows researchers to selectively isolate and study circRNAs from total RNA preparations, advancing our understanding of non-coding RNA regulation and function.
- In summary, RNase R is a unique and functionally versatile exoribonuclease critical for the degradation of structured RNA molecules. Its roles in RNA surveillance, stress response, and ribosome processing underscore its biological importance. Furthermore, its enzymatic specificity makes it a powerful tool in RNA-based research, particularly in the study of circular RNAs and RNA stability.
