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

ABSTRACT: The Lupus autoantigen La prevents mis-channeling of tRNA fragments into the human microRNA pathway

PROVIDER: PRJNA311969 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR3092114.fastq.gz	Fastqsanger.gz
	SRR3092115.fastq.gz	Fastqsanger.gz
	SRR3092116.fastq.gz	Fastqsanger.gz
	SRR3092117.fastq.gz	Fastqsanger.gz
	SRR3167671.fastq.gz	Fastqsanger.gz

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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.

2016-06-22 | GSE77897 | GEO

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

2016-06-22 | GSE76676 | GEO

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

Project description:This SuperSeries is composed of the SubSeries listed below.

2016-06-22 | GSE77898 | GEO

Homo sapiens

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

| PRJNA308305 | ENA

Homo sapiens

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

| PRJNA311970 | ENA

Autoantigen promotes progression to aggressive TCL1 leukemia

Project description:Activated BCR signaling in Murine CLL leukemia cells responsive to autoantigen phosphatidylcholine Murine CLL cells obtained from spleen and peritoneum were compared for the genetic signatures associated with autoantigen responsiveness

2013-05-01 | E-GEOD-45481 | biostudies-arrayexpress

Comparision of La-RNA-binding between wild type La and sumoylation deficient La mutant (K41/200R) in HEK293 cells.

Project description:We performed a RNA immunoprecipitations experiments using gfp-specific antibodies to precipitate gfp-tagged La proteins from from gfp-La wild type and sumoylation deficient La mutant (K41/200R) cells and found that specific mRNAs are preferentially enriched gfp-La wild type RIPs when compared to sumoylation deficient La mutant (K41/200R) RIPs.

2017-11-22 | GSE102842 | GEO

An altered basis of tRNA processing is linked to a distinct La protein in T. thermophila

Project description:La proteins bind the UUU-3’OH sequence found at the 3’-end of nascent RNA polymerase III transcripts, including pre-tRNAs, using a tandem arrangement of a winged-helix fold La motif (LaM) and an adjacent RNA recognition motif (RRM). La binding in diverse species results in protection of the 3’-end from exonucleases, stabilization of the pre-tRNA species and promotion of pre-tRNA folding until the UUU-3’OH containing trailer is endonucleolytically cleaved. Based on sequence conservation in the LaM, the Tetrahymena thermophila protein MLP1 (and related factors in other alveolates) has been hypothesized to function as a genuine La protein, despite the absence of the adjacent RRM found in La proteins of all prior investigated species. We show that MLP1 functions as a genuine La protein in that it binds and affects the processing of pre-tRNAs in T. thermophila and when expressed as a heterologous factor in fission yeast, however, unlike in other examined eukaryotes, depletion of MLP1 results in 3’-trailer stabilization. We also observed that 3’-trailers in T. thermophila are uniquely shortened relative to other examined eukaryotes, and that 5’-leaders in this species have evolved to disfavour pre-tRNA leader/trailer pairing. Our data suggest that the variant MLP1 architecture relative to other genuine La proteins is linked to an altered mechanism of tRNA processing in T. thermophila.

2022-09-13 | GSE199642 | GEO

Regulation of La/SSB-dependent viral gene expression by pre-tRNA 3' trailer-derived tRNA fragments.

Project description:tRNA-derived RNA fragments (tRFs) have emerged as a new class of functional RNAs implicated in cancer, metabolic and neurological disorders, and viral infection. Yet our understanding of their biogenesis and functions remains limited. In the present study, through analysis of small RNA profile we have identified a distinct set of tRFs derived from pre-tRNA 3' trailers in the hepatocellular carcinoma cell line Huh7. Among those tRFs, tRF_U3_1, which is a 19-nucleotide-long chr10.tRNA2-Ser(TGA)-derived trailer, was expressed most abundantly in both Huh7 and cancerous liver tissues, being present primarily in the cytoplasm. We show that genetic loss of tRF_U3_1 does not affect cell growth and it is not involved in Ago2-mediated gene silencing. Using La/SSB knockout Huh7 cell lines, we demonstrate that this nuclear-cytoplasmic shuttling protein directly binds to the 3' U-tail of tRF_U3_1 and other abundantly expressed trailers and plays a critical role in their stable cytoplasmic accumulation. The pre-tRNA trailer-derived tRFs capable of sequestering the limiting amounts of La/SSB in the cytoplasm rendered cells resistant to various RNA viruses, which usurp La/SSB with RNA chaperone activity for their gene expression. Collectively, our results establish the trailer-derived tRF-La/SSB interface, regulating viral gene expression.

| S-EPMC6765225 | biostudies-literature

Autoantigen promotes progression to aggressive TCL1 leukemia

Project description:Activated BCR signaling in Murine CLL leukemia cells responsive to autoantigen phosphatidylcholine

2013-05-01 | GSE45481 | GEO