What Is an Endoribonuclease and What Does It Do?

An endoribonuclease is an enzyme that cuts ribonucleic acid (RNA). Found in all forms of life, they perform numerous housekeeping and regulatory tasks. They cleave the phosphodiester bonds linking the building blocks of an RNA molecule. This internal cutting action is fundamental to cellular processes that depend on precise RNA management. Their activities ensure RNA molecules are correctly shaped, transported, and recycled.

Defining Endoribonuclease Action

The prefix “endo” signifies that the enzyme makes cuts within the RNA strand, distinguishing them from exoribonucleases that remove nucleotides from the ends. An endoribonuclease recognizes a specific sequence or three-dimensional structure on an RNA molecule. Once bound, it breaks a phosphodiester bond, cutting the strand into smaller pieces for further processing or degradation.

Essential Cellular Functions of Endoribonucleases

One primary function is the maturation of non-coding RNA molecules like ribosomal RNA (rRNA). These molecules are transcribed as long, inactive precursors that must be cut to their functional size. Endoribonucleases perform these cuts, allowing rRNA to be assembled into ribosomes, the cell’s protein-building machinery.

Endoribonucleases regulate gene expression by initiating the breakdown of messenger RNA (mRNA). These enzymes control the lifespan of mRNA, which carries genetic instructions from DNA to the ribosomes. This determines how much protein is produced from a gene. This process removes old or damaged mRNAs, allowing the cell to change its protein production in response to new signals.

These enzymes also serve as a quality control system by eliminating defective RNA. For example, if an mRNA contains a premature stop signal, it could produce a harmful protein. Surveillance pathways like nonsense-mediated decay (NMD) use endoribonucleases to destroy these faulty mRNAs before they are translated.

Notable Types and Their Specific Tasks

One notable example is RNase P, a ribozyme whose catalytic component is made of RNA. RNase P performs a single, precise cut to generate the mature 5′ end of all transfer RNA (tRNA) molecules. This modification is required for them to function in protein synthesis and is conserved across all domains of life.

Drosha and Dicer are central to the RNA interference (RNAi) pathway. Working in the nucleus, Drosha makes the first cut on primary microRNA (pri-miRNA) transcripts. The resulting precursor is exported to the cytoplasm, where Dicer makes a second cut to produce mature microRNA (miRNA). These small miRNAs then regulate gene expression by silencing specific mRNAs.

The RNase III family, which includes Drosha and Dicer, cleaves double-stranded RNA (dsRNA). In bacteria, an RNase III enzyme helps mature ribosomal RNA. In humans, the endoribonuclease RNase L is part of the innate immune system. Activated during viral infection, it degrades both viral and cellular RNA to halt protein synthesis and inhibit viral replication.

Implications for Human Health and Disease

Malfunction of endoribonucleases is linked to various human diseases. Mutations in the genes coding for these enzymes can cause genetic disorders. For instance, mutations affecting the tRNA splicing endonuclease complex lead to pontocerebellar hypoplasia, a neurodegenerative disorder. The improper processing of tRNA disrupts protein synthesis, which is especially harmful to developing neurons.

The role of these enzymes in gene regulation connects them to cancer. Dysregulation of miRNA processing enzymes like Drosha and Dicer alters the levels of miRNAs that control cell growth and survival. These endoribonucleases can act as either tumor suppressors or oncogenes. For example, reduced Dicer expression is observed in some cancers and is associated with a poor prognosis.

Endoribonucleases are involved in the conflict between host cells and viruses. As part of the innate immune response, RNase L degrades viral RNA to limit infection. Conversely, many viruses have their own endoribonucleases, like Nsp15, to counteract host defenses. Misregulation of RNA degradation can also lead to an accumulation of self-RNA, potentially triggering an autoimmune response.

Endoribonucleases in Research and Technology

The precise cutting ability of endoribonucleases makes them useful tools in research. A prominent application is RNA interference (RNAi), which uses the cell’s machinery, including Dicer, to silence specific genes. Researchers introduce synthetic double-stranded RNA matching a target gene. Dicer processes this into small interfering RNAs (siRNAs) that guide the degradation of the corresponding mRNA, turning the gene off.

The CRISPR-Cas system also utilizes these enzymes. While Cas9 is known for DNA editing, the related Cas13 is an RNA-guided endoribonuclease. Researchers can program Cas13 with a guide RNA to cut a specific target RNA. This can be used to knock down gene expression, track RNA in live cells, or edit RNA to correct genetic defects. The temporary nature of RNA editing offers a reversible alternative to permanent DNA editing.

The specificity of these enzymes makes them valuable in diagnostics. The Cas13-based SHERLOCK platform, for example, can detect minute amounts of viral or bacterial nucleic acids. In this system, a Cas13 enzyme recognizes a target RNA, which activates its “collateral cleavage” activity. This causes it to cut nearby reporter molecules, generating a detectable signal. This technology has been adapted for rapid tests for pathogens and genetic mutations.