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The Lupus autoantigen La prevents mis-channeling of tRNA fragments into the human microRNA pathway [miRNA-seq]

ABSTRACT: The Lupus autoantigen (La) is a single-stranded RNA-binding protein that stabilizes RNA polymerase III (pol III) transcripts and supports RNA folding. In addition, La has been implicated in different steps of the mammalian small RNA pathway. Here, we have analyzed effects of La depletion on the Argonaute (Ago)-bound small RNAs in human cells. We find that in the absence of La, distinct tRNA fragments are loaded into Ago protein complexes and our data suggests that La prevents the production and loading of such tRNA fragments. However, one specific isoleucine tRNA escapes this regulation and produces both a functional tRNA as well as a microRNA (miRNA). We demonstrate that 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. Thus, La functions as gatekeeper to ensure correct tRNA generation and to protect the miRNA pathway from potentially functional tRNA fragments.

ORGANISM(S): Homo sapiens

PROVIDER: GSE76676 | GEO | 2016/06/22

SECONDARY ACCESSION(S): PRJNA308305

REPOSITORIES: GEO

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The Lupus autoantigen La prevents mis-channeling of tRNA fragments into the human microRNA pathway [PAR-CLIP]

Project description:The Lupus autoantigen (La) is a single-stranded RNA-binding protein that stabilizes RNA polymerase III (pol III) transcripts and supports RNA folding. In addition, La has been implicated in different steps of the mammalian small RNA pathway. Here, we have analyzed effects of La depletion on the Argonaute (Ago)-bound small RNAs in human cells. We find that in the absence of La, distinct tRNA fragments are loaded into Ago protein complexes and our data suggests that La prevents the production and loading of such tRNA fragments. However, one specific isoleucine tRNA escapes this regulation and produces both a functional tRNA as well as a microRNA (miRNA). We demonstrate that 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. Thus, La functions as gatekeeper to ensure correct tRNA generation and to protect the miRNA pathway from potentially functional tRNA fragments.

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