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. 2023 Mar 7;14:1112513. doi: 10.3389/fimmu.2023.1112513

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Copyright © 2023 Hewavisenti, Arena, Ahlenstiel and Sasson

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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RNAi pathways. Post Transcriptional Gene Silencing (PTGS) inducing short interfering ribonucleic acid (siRNA) operate via the actions of the ribonucleic acid (RNA) induced silencing complex (RISC), a multiprotein nuclease complex comprised of Argonaute-2 (Ago-2), Dicer, TAR RNA binding protein, protein kinase interferon-inducible double stranded RNA dependent activator, and GW domain protein 182 in humans. The antisense strand binds Ago-2 and is incorporated into the RISC complex. The antisense strand guides the complex to the targeted mRNA product, where Ago-2 facilitates the cleavage of, and subsequent degradation of the messenger ribonucleic acid (mRNA). Transcriptional Gene Silencing (TGS) inducing siRNA operate via the actions of the RNA induced transcriptional silencing (RITS) complex, a multiprotein complex comprised of Argonaute-1 (Ago-1) and other, yet unidentified, proteins in humans. The antisense strand binds Ago-1 and is incorporated into the RITS complex, where it guides the complex into the cell nucleus and targets the gene promoter. Heritable epigenetic modifications result in compaction of chromatin structures surrounding the target site, preventing the transcription of gene products, and silencing expression. Created with BioRender.com.