Abstract
The Argonaute (AGO) and the Trinucleotide Repeat Containing 6 (TNRC6) family proteins are the core components of the mammalian microRNA-induced silencing complex (miRISC), the machinery that mediates microRNA function in the cytoplasm. The cytoplasmic miRISC-mediated post-transcriptional gene repression has been established as the canonical mechanism through which AGO and TNRC6 proteins operate. However, growing evidence points towards an additional mechanism through which AGO and TNRC6 regulate gene expression in the nucleus. While several mechanisms through which miRISC components function in the nucleus have been described, in this review we aim to summarize the major findings that have shed light on the role of AGO and TNRC6 in mammalian chromatin biology and on the implications these novel mechanisms may have in our understanding of regulating gene expression.
Highlights
Most of the mammalian genome is transcribed into non-coding RNAs that play a variety of structural and regulatory roles in cells
This leads to a higher degree of binding specificity than that allowed by proteins, which instead rely on a limited number of binding domains to recognize DNA and RNA sequences
For example: (1) What are the determinants that drive either transcriptional gene activation (TGA) or transcriptional gene silencing (TGS) on a given target gene? (2) What is the relative contribution of the AGO1-4 paralogues in the silencing or activating process? (3) Is AGO2’s slicing activity required? (4) Does the size RNAs (sRNAs) recognize the DNA sequence or a nascent transcript? (5) To what extent is DNA methylation involved in the silencing process?
Summary
Most of the mammalian genome is transcribed into non-coding RNAs (ncRNAs) that play a variety of structural and regulatory roles in cells. Small-size RNAs (sRNAs), ranging from ~18 to 30 nucleotides, are a well-known class of ncRNAs involved in both the cytoplasmic and nuclear regulation of gene functions Their primary sequence provides the information necessary to guide repressor or activator complexes to complementary binding sites within a target nucleic acid. PiRNAs associate with PIWI proteins, while miRs and endo-siRNAs associate with AGOs In each of these complexes, the role of Argonaute is to promote the proper steric conditions to favor base pairing between the sRNA and the target site [6], thereby enabling sRNA-mediated regulatory processes (reviewed in [4]). We will mention the piRNA pathway, where the PIWI clade of Argonautes mediates the silencing of transposons in the germline through wellcharacterized epigenetic mechanisms similar to those mediated by the AGOs in the soma
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
