[Frontiers in Bioscience, Landmark, 25, 1-42, Jan 1, 2020]

AGO unchained: Canonical and non-canonical roles of Argonaute proteins in mammals

Laura Sala1, Srividya Chandrasekhar1, Joana A. Vidigal1

1Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, Bethesda, MD 20892, USA


1. Abstract
2. A Long Evolutionary Road for Argonaute Proteins
3. Not all AGOs are created equal
4. Biogenesis of Small RNA guides in mammals
5. Small-RNA loading and sorting into AGO proteins
6. RISC assembly and gene regulation by miRNAs
7. Argonaute catalytic activity in mammals
8. Argonautes in the nucleus
9. Functional specification beyond catalysis
10. Concluding Remarks
11. Acknowledgments
12. References


Argonaute (AGO) proteins play key roles in animal physiology by binding to small RNAs and regulating the expression of their targets. In mammals, they do so through two distinct pathways: the miRNA pathway represses genes through a multiprotein complex that promotes both decay and translational repression; the siRNA pathway represses transcripts through direct Ago2-mediated cleavage. Here, we review our current knowledge of mechanistic details and physiological requirements of both these pathways and briefly discuss their implications to human disease.


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Key Words: microRNAs, endo-siRNAs, Argonaute, mammals, In Vivo, Review

Send correspondence to: Joana A. Vidigal, Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, Bethesda, MD 20892, USA, Tel: 240-760-6691, E-mail: joana.vidigal@nih.gov