Hasler, Daniele and Lehmann, Gerhard and Murakawa, Yasuhiro and Klironomos, Filippos and Jakob, Leonhard and Graesser, Friedrich A. and Rajewsky, Nikolaus and Landthaler, Markus and Meister, Gunter (2016) The Lupus Autoantigen La Prevents Mis-channeling of tRNA Fragments into the Human MicroRNA Pathway. MOLECULAR CELL, 63 (1). pp. 110-124. ISSN 1097-2765, 1097-4164
Full text not available from this repository. (Request a copy)Abstract
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 50 leader and 30 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ARGONAUTE PROTEIN COMPLEXES; CHAPERONE ACTIVITY; GENE-EXPRESSION; NONCODING RNA; RECOGNITION; BIOGENESIS; PRECURSORS; CATALYSIS; REVEALS; SNORNAS; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I > Prof. Dr. Gunter Meister |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Apr 2019 11:52 |
| Last Modified: | 02 Apr 2019 11:52 |
| URI: | https://pred.uni-regensburg.de/id/eprint/3638 |
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