4.8 Review

Anatomy of four human Argonaute proteins

Journal

NUCLEIC ACIDS RESEARCH
Volume 50, Issue 12, Pages 6618-6638

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/nar/gkac519

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Funding

  1. NIH [R01GM124320, R01GM138997]

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This review explores the completed structural catalog of the four AGO proteins, describing their common features and differences in target specificity, and emphasizing the unique roles of each AGO.
MicroRNAs (miRNAs) bind to complementary target RNAs and regulate their gene expression post-transcriptionally. These non-coding regulatory RNAs become functional after loading into Argonaute (AGO) proteins to form the effector complexes. Humans have four AGO proteins, AGO1, AGO2, AGO3 and AGO4, which share a high sequence identity. Since most miRNAs are found across the four AGOs, it has been thought that they work redundantly, and AGO2 has been heavily studied as the exemplified human paralog. Nevertheless, an increasing number of studies have found that the other paralogs play unique roles in various biological processes and diseases. In the last decade, the structural study of the four AGOs has provided the field with solid structural bases. This review exploits the completed structural catalog to describe common features and differences in target specificity across the four AGOs.

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