The Lupus Autoantigen La Prevents Mis-channeling of tRNA Fragments into the Human MicroRNA Pathway
| Autor: | Nikolaus Rajewsky, Leonhard Jakob, Yasuhiro Murakawa, Gerhard Lehmann, Daniele Hasler, Markus Landthaler, Filippos Klironomos, Friedrich A. Grässer, Gunter Meister |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Ribonuclease III Herpesvirus 4 Human Biology Karyopherins Transfection XPO5 Autoantigens RNA polymerase III DEAD-box RNA Helicases 03 medical and health sciences Structure-Activity Relationship RNA interference microRNA RNA Precursors Humans RNA Processing Post-Transcriptional RNA Transfer Ile Molecular Biology Binding Sites RNA RNA Polymerase III Cell Biology Hep G2 Cells Argonaute Molecular biology MicroRNAs 030104 developmental biology HEK293 Cells Ribonucleoproteins A549 Cells Transfer RNA Argonaute Proteins biology.protein MCF-7 Cells Nucleic Acid Conformation RNA Viral RNA Interference Dicer HeLa Cells Protein Binding |
| Zdroj: | Molecular Cell |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/j.molcel.2016.05.026 |
| Popis: | The Lupus autoantigen La is an RNA-binding protein that stabilizes RNA polymerase III (Pol III) transcripts and supports RNA folding and has in addition been implicated in the mammalian microRNA (miRNA) pathway. Here, we have analyzed effects of La depletion on Argonaute (Ago)-bound small RNAs in human cells. We find that in the absence of La, distinct tRNA fragments are loaded into Ago proteins. Thus, La functions as gatekeeper ensuring correct tRNA maturation and protecting the miRNA pathway from potentially functional tRNA fragments. However, one specific isoleucin pre-tRNA produces both a functional tRNA and a miRNA even when La is present. We demonstrate that the fully complementary 5' leader and 3' trailer of the pre-tRNA-Ile form a double-stranded RNA molecule that has low affinity to La. Instead, Exportin-5 (Xpo5) recognizes it as miRNA precursor and transports it into the cytoplasm for Dicer processing and Ago loading. |
| Databáze: | OpenAIRE |
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