Endogenous Ribonucleases: Therapeutic Targeting of the Transcriptome Through Oligonucleotide-Triggered RNA Inactivation

TL;DR

This paper reviews how RNA-targeting enzymes can be used to control gene expression for therapeutic purposes.

Contribution

The paper provides a comprehensive analysis of RNA modulation mechanisms involving endogenous ribonucleases and their therapeutic potential.

Findings

Antisense oligonucleotides and RNA mimics interact with enzymes like RNase H1 and AGO to regulate RNA.

Structural and functional features of endonucleases influence their therapeutic effectiveness.

RNA interference and antisense pathways offer strategies for disease-specific RNA targeting.

Abstract

The selective regulation of gene expression at the RNA level represents a rapidly evolving field offering substantial clinical potential. This review examines the molecular mechanisms of intracellular enzymatic systems that utilize single-stranded nucleic acids to downregulate specific RNA targets. The analysis encompasses antisense oligonucleotides and synthetic mimics of small interfering RNA (siRNA), microRNA (miRNA), transfer RNA-derived small RNA (tsRNA), and PIWI-interacting RNA (piRNA), elucidating their intricate interactions with crucial cellular machinery, specifically RNase H1, RNase P, AGO, and PIWI proteins, mediating their biological effects. The functional and structural characteristics of these endonucleases are examined in relation to their mechanisms of action and resultant therapeutic outcomes. This comprehensive analysis illuminates the interactions between single-stranded nucleic acids and their endonuclease partners, covering antisense inhibition pathways as well as RNA interference processes. This field of research has important implications for advancing targeted RNA modulation strategies across various disease contexts.

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