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Mol Cell. 2016 Jul 7;63(1):110-24. doi: 10.1016/j.molcel.2016.05.026. Epub 2016 Jun 23.

The Lupus Autoantigen La Prevents Mis-channeling of tRNA Fragments into the Human MicroRNA Pathway.

Author information

1
Biochemistry Center Regensburg (BZR), Laboratory for RNA Biology, University of Regensburg, Regensburg 93053, Germany.
2
Laboratory for RNA Biology and Posttranscriptional Regulation, Berlin Institute for Medical Systems Biology, Max-Delbrück Center for Molecular Medicine, Berlin 13125, Germany.
3
Laboratory for Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max-Delbrück Center for Molecular Medicine, Berlin 13125, Germany.
4
Institute of Virology, Saarland University Medical School, Homburg/Saar 66421, Germany.
5
Biochemistry Center Regensburg (BZR), Laboratory for RNA Biology, University of Regensburg, Regensburg 93053, Germany. Electronic address: gunter.meister@vkl.uni-regensburg.de.

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.

PMID:
27345152
DOI:
10.1016/j.molcel.2016.05.026
[Indexed for MEDLINE]
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