- Endoribonucleases are enzymes that catalyze the internal cleavage of RNA molecules by hydrolyzing the phosphodiester bonds within the RNA strand. Unlike exoribonucleases, which remove nucleotides from the ends of RNA, endoribonucleases cut at specific internal sites, generating RNA fragments with distinct 5′ and 3′ termini. These enzymes play central roles in RNA metabolism, including RNA processing, maturation, decay, and quality control in both prokaryotic and eukaryotic cells.
- Endoribonucleases can be broadly categorized based on substrate specificity and sequence preference. Some, like RNase A, exhibit base-specific cleavage (e.g., at pyrimidine residues), while others such as RNase T1 and RNase U2 cleave specifically at guanine or adenine residues, respectively. Still others, like RNase III, recognize and cleave double-stranded RNA (dsRNA), playing a key role in rRNA maturation and RNA interference (RNAi) pathways.
- In eukaryotes, endoribonucleases are involved in diverse biological processes such as the splicing of pre-mRNA, cleavage of rRNA and tRNA precursors, and regulation of mRNA stability. A well-known example is Ire1, an ER stress sensor with endoribonuclease activity that cleaves XBP1 mRNA during the unfolded protein response. In bacteria, enzymes like RNase E and RNase III are essential for RNA degradation and maturation of RNA transcripts.
- Endoribonucleases are also widely used as research tools for probing RNA structure, mapping RNA cleavage sites, and studying RNA-protein interactions. Some are employed in diagnostic assays and emerging therapeutic strategies, such as programmable RNA-guided nucleases for targeting disease-related RNAs.
- In summary, endoribonucleases are critical regulators of RNA lifecycle and function. Their substrate specificity and catalytic versatility make them indispensable in both cellular biology and molecular biotechnology.
