AI Article Synopsis
- - Argonaute proteins bind small RNAs to cut complementary target RNAs, with human Ago4 being catalytically inactive despite its similarity to the active Ago2.
- - Researchers created chimeras of Ago2 and Ago4 to identify features responsible for Ago4's inactivity, focusing on the catalytic center and specific sequence elements.
- - Phylogenetic analysis reveals that the evolutionary relationship among Ago proteins does not completely match the structural changes that cause inactivity, indicating possible functional adaptations among them.
Article Abstract
Argonaute proteins bind small RNAs and mediate cleavage of complementary target RNAs. The human Argonaute protein Ago4 is catalytically inactive, although it is highly similar to catalytic Ago2. Here, we have generated Ago2-Ago4 chimeras and analyzed their cleavage activity in vitro. We identify several specific features that inactivate Ago4: the catalytic center, short sequence elements in the N-terminal domain, and an Ago4-specific insertion in the catalytic domain. In addition, we show that Ago2-mediated cleavage of the noncanonical miR-451 precursor can be carried out by any catalytic human Ago protein. Finally, phylogenetic analyses establish evolutionary distances between the Ago proteins. Interestingly, these distances do not fully correlate with the structural changes inactivating them, suggesting functional adaptations of individual human Ago proteins.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4174435 | PMC |
| http://dx.doi.org/10.1261/rna.045203.114 | DOI Listing |
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