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Identification of functional tetramolecular RNA G-quadruplexes derived from transfer RNAs.

ABSTRACT: RNA G-quadruplex (RG4) structures are involved in multiple biological processes. Recent genome-wide analyses of human mRNA transcriptome identified thousands of putative intramolecular RG4s that readily assemble in vitro but shown to be unfolded in vivo. Previously, we have shown that mature cytoplasmic tRNAs are cleaved during stress response to produce tRNA fragments that function to repress translation in vivo. Here we report that these bioactive tRNA fragments assemble into intermolecular RG4s. We provide evidence for the formation of uniquely stable tetramolecular RG4 structures consisting of five tetrad layers formed by 5'-terminal oligoguanine motifs of an individual tRNA fragment. RG4 is required for functions of tRNA fragments in the regulation of mRNA translation, a critical component of cellular stress response. RG4 disruption abrogates tRNA fragments ability to trigger the formation of Stress Granules in vivo. Collectively, our data rationalize the existence of naturally occurring RG4-assembling tRNA fragments and emphasize their regulatory roles.

SUBMITTER: Lyons SM

PROVIDER: S-EPMC5655342 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Identification of functional tetramolecular RNA G-quadruplexes derived from transfer RNAs.

Lyons Shawn M SM Gudanis Dorota D Coyne Steven M SM Gdaniec Zofia Z Ivanov Pavel P

Nature communications 20171024 1

RNA G-quadruplex (RG4) structures are involved in multiple biological processes. Recent genome-wide analyses of human mRNA transcriptome identified thousands of putative intramolecular RG4s that readily assemble in vitro but shown to be unfolded in vivo. Previously, we have shown that mature cytoplasmic tRNAs are cleaved during stress response to produce tRNA fragments that function to repress translation in vivo. Here we report that these bioactive tRNA fragments assemble into intermolecular RG ...[more]

PMID: 29066746

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Project description:Background: IgA nephropathy (IgAN) is one of the most common forms of primary glomerulonephritis. Recent studies have indicated that small noncoding RNAs, such as tRNA-derived small RNAs (tsRNAs), might be novel biomarkers for glomerulonephritis. We therefore investigated the potential roles and possible functions of the tsRNAs in IgAN.Method: Peripheral blood mononuclear cells (PBMCs) were extracted from blood samples of the patients with IgAN and healthy control groups. The expression profiles of tsRNAs were assessed by small RNA sequencing (RNA-Seq) in PBMCs of the IgAN and control groups. Dysregulated tsRNAs were selected for validation by quantitative real-time polymerase chain reaction (qRT-PCR). Target gene prediction and enrichment were performed by bioinformatics analysis.Results: The results revealed that 143 significantly upregulated and 202 significantly downregulated tsRNAs were differentially altered in the IgAN group compared with the control group. Five upregulated tsRNAs (tRF-Val-AAC-007, tRF-Ala-AGC-063, tRF-Gln-CTG-010, tRF-Tyr-GTA-011 and tRF-Thr-AGT-007) and 3 downregulated tsRNAs (tiRNA-Val-TAC-004, tRF-Gly-CCC-005 and tRF-His-GTG-006) were selected for validation by qRT-PCR; the results were consistent with the sequencing data. Gene Ontology (GO) analysis revealed that the target genes predicted by upregulated tsRNAs were mostly enriched in "nucleic acid metabolic process,' "intracellular part,' and "ion binding,' whereas the target genes predicted by downregulated tsRNAs were mostly enriched in "regulation of cellular component organization,' "membrane-bound organelle,' and "ion binding.' Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the target genes predicted by upregulated tsRNAs were mostly enriched in "herpes simplex virus 1 infection,' whereas the target genes predicted by downregulated tsRNAs were mostly enriched in "circadian rhythm CONCLUSIONS:: The present study confirmed the differential expression of tsRNAs in patients with IgAN, and these dysregulated tsRNAs might be novel potential targets for the diagnosis and treatment of IgAN.

Dataset Information

Identification of functional tetramolecular RNA G-quadruplexes derived from transfer RNAs.

Publications

Identification of functional tetramolecular RNA G-quadruplexes derived from transfer RNAs.

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