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The Lupus autoantigen La prevents Mis-channeling of tRNA fragments into the human microRNA pathway

Item Type:Article
Title:The Lupus autoantigen La prevents Mis-channeling of tRNA fragments into the human microRNA pathway
Creators Name:Hasler, D. and Lehmann, G. and Murakawa, Y. and Klironomos, F. and Jakob, L. and Graesser, F.A. and Rajewsky, N. and Landthaler, M. and Meister, G.
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 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.
Keywords:A549 Cells, Argonaute Proteins, Autoantigens, Binding Sites, DEAD-box RNA Helicases, HEK293 Cells, HeLa Cells, Hep G2 Cells, Human Herpesvirus 4, Karyopherins, MCF-7 Cells, MicroRNAs, Nucleic Acid Conformation, Post-Transcriptional RNA Processing, Protein Binding, RNA Interference, RNA Polymerase III, RNA Precursors, Ribonuclease III, Ribonucleoproteins, Structure-Activity Relationship, Transfection, Transfer RNA Ile, Viral RNA
Source:Molecular Cell
ISSN:1097-2765
Publisher:Cell Press / Elsevier (U.S.A.)
Volume:63
Number:1
Page Range:110-124
Date:7 July 2016
Official Publication:https://doi.org/10.1016/j.molcel.2016.05.026
PubMed:View item in PubMed

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