Molecular Biology Transcriptomics

RNA Degradation

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RNA decay is the process in which ribonucleic acid (RNA) molecules are enzymatically degraded. RNA decay is a regulated event and serves to control levels of particular RNA molecules. A specific example is nonsense-mediated mRNA decay (NMD), a process that removes transcripts containing premature stop codons.

In all organisms tested from all kingdoms of life, RNA degradation is a frequent activity. Overall, the emerging picture is that despite the immense complexity of specific RNA degradation pathways, there are real similarities in the basics of RNA degradation between bacteria, archaea, and eukaryotes, underlining its major, and long-standing, importance.

There are three major classes of intracellular RNA-degrading enzymes (ribonucleases or RNases);

  • endonucleases that cut RNA internally
  • 5′ exonucleases that hydrolyze RNA from the 5′ end
  • 3′ exonucleases that degrade RNA from the 3′ end

Endo and 3′ exonucleases have long been characterized in all domains of life, whereas 5′ exonucleases were, until recently, believed to be absent from bacteria.

Most genomes encode abundance of RNases, often with overlapping activities, making redundancy a general feature of RNA degradation systems. 

Many of the enzymes and cofactors involved in RNA processing and degradation are multifunctional. In yeast, for example, both the 5′ exonuclease Rat1 and the 3′ exonucleases of the exosome complex not only target and degrade RNAs transcribed by RNA polymerases I, II, and III but also function in RNA-processing reactions that generate the mature termini of stable RNA species. Similarly, in bacteria the same factors participate in RNA maturation and in the degradation of both stable RNAs and messenger RNAs (mRNAs).

Such dual functions need that a single enzyme can precisely process some RNA species to generate defined ends while holding on to the capacity to degrade other RNAs entirely even the same RNAs under different circumstances.

This multiplicity of function that characterizes ribonucleases in both bacteria and eukaryotes underlines the key importance of mechanisms that specifically identify and target aberrant RNAs and RNA-protein complexes. This specificity is frequently conferred by cofactors, of which many have been identified.

RNA degradation ensures appropriate levels of mRNA transcripts within cells and eliminates aberrant RNAs. Detailed studies of RNA degradation dynamics have been heretofore infeasible because of the inherent instability of degradation intermediates due to the high processivity of the enzymes involved. To see decay intermediates and to characterize the spatiotemporal dynamics of mRNA decay, a set of methods that apply XRN1-resistant RNA sequences (xrRNAs) have been developed to protect mRNA transcripts from 5′–3′ exonucleolytic digestion.

Stable RNA is also degraded in response to certain agents that change membrane permeability. The extensive degradation that accompanies such treatment is probably due to loss of ions, such as Mg 2+, which help to stabilize ribosome structure, and to the entry of RNase I into the cell cytoplasm. 

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