Structural Flexibility Enables Alternative Maturation, ARGONAUTE Sorting and Activities of miR168, a Global Gene Silencing Regulator in Plants
| Autor: | Christopher A. Brosnan, Frédéric H.-T. Allain, Taichiro Iki, Nicolás G. Bologna, Nathan Pumplin, Olivier Voinnet, Alexis Sarazin, Antoine Cléry |
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| Rok vydání: | 2018 |
| Předmět: |
0106 biological sciences
0301 basic medicine Arabidopsis Regulator Cellular homeostasis Plant Science Computational biology 01 natural sciences Tombusvirus 03 medical and health sciences Gene Expression Regulation Plant microRNA Gene silencing Gene Silencing Molecular Biology biology Arabidopsis Proteins Effector fungi Argonaute biology.organism_classification MicroRNAs 030104 developmental biology RNA Plant Argonaute Proteins biology.protein 010606 plant biology & botany Dicer |
| Zdroj: | Molecular Plant. 11:1008-1023 |
| ISSN: | 1674-2052 |
| DOI: | 10.1016/j.molp.2018.05.006 |
| Popis: | In eukaryotes, the RNase-III Dicer often produces length/sequence microRNA (miRNA) variants, called "isomiRs", owing to intrinsic structural/sequence determinants of the miRNA precursors (pre-miRNAs). In this study, we combined biophysics, genetics and biochemistry approaches to study Arabidopsis miR168, the key feedback regulator of central plant silencing effector protein ARGONAUTE1 (AGO1). We identified a motif conserved among plant pre-miR168 orthologs, which enables flexible internal base-pairing underlying at least three metastable structural configurations. These configurations promote alternative, accurate Dicer cleavage events generating length and structural isomiR168 variants with distinctive AGO sorting properties and modes of action. Among these isomiR168s, a duplex with a 22-nt guide strand exhibits strikingly preferential affinity for AGO10, the closest AGO1 paralog. The 22-nt miR168-AGO10 complex antagonizes AGO1 accumulation in part via "transitive RNAi", a silencing-amplification process, to maintain appropriate AGO1 cellular homeostasis. Furthermore, we found that the tombusviral P19 silencing-suppressor protein displays markedly weaker affinity for the 22-nt form among its isomiR168 cargoes, thereby promoting AGO10-directed suppression of AGO1-mediated antiviral silencing. Taken together, these findings indicate that structural flexibility, a previously overlooked property of pre-miRNAs, considerably increases the versatility and regulatory potential of individual MIRNA genes, and that some pathogens might have evolved the capacity or mechanisms to usurp this property. |
| Databáze: | OpenAIRE |
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