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Detection of the tRNA-derived fragments in human pancreatic islets of control individuals

ABSTRACT: Detection of the tRNA-derived fragments in human pancreatic islets of control individuals

PROVIDER: PRJNA1079232 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28047223.fastq.gz	Fastqsanger.gz
	SRR28047224.fastq.gz	Fastqsanger.gz
	SRR28047225.fastq.gz	Fastqsanger.gz
	SRR28047226.fastq.gz	Fastqsanger.gz
	SRR28047227.fastq.gz	Fastqsanger.gz

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Detection of the tRNA-derived fragments in human pancreatic islets of control individuals

Project description:Cytosolic and mitochondrial fragments that arise from the cleavage of tRNAs and mt-tRNAs, respectively, have been identified as potential novel regulators of cellular functions. In this study we identified hundreds of fragments in the pancreatic islets of healthy human individuals. We were able to annotate 3593 tRFs (16-55 base pairs) present in the islets of healthy human individuals (we considered a minimum of 5 cpm values in each of the 3 samples). Interestingly, the vast majority of the tRFs whose levels are altered in pancreatic islets of prediabetic NOD mice and in extracellular vesicles released by activated CD4+ T lymphocytes, are conserved in humans and were detected in human pancreatic islets. This suggests a possible conservation of the findings of this study in a human context.

2024-05-14 | GSE256343 | GEO

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Processing by RNase 1 forms tRNA halves and distinct Y RNA fragments in the extracellular environment

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Project description:tRNAArg-derived fragments mediate protein arginylation [tRNA]

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Study of the tRNA-derived fragment expression profile in mouse pancreatic islets of pre-diabetic obese db/db mice

Project description:In this study, we discovered cytosolic and mitochondrial fragments resulting from tRNA and mt-tRNA cleavage, which may act as new regulators of cellular and metabolic functions. We analyzed hundreds of these fragments in the pancreatic islets of db/db mice and compared them to heterozygous control db/+ mice. At 16 weeks of age, db/db mice exhibit obesity, insulin resistance, and glucose intolerance. In our analysis, we identified 3858 tRFs in the islets of db/db mice, among which 342 exhibited significant changes (≥ 2 fold; adjusted p value ≤ 0.05) compared to controls. Of these, 199 tRFs showed increased levels, while 170 tRFs showed decreased levels in the pre-diabetic mice. Notably, a striking majority (147 out of 170) of the tRFs with reduced abundance in the islets of db/db mice were derived from the cleavage of tRNAs encoded by the mitochondrial genome. Our findings reveal a significant reshaping of mitochondrial tRFs in pre-diabetic conditions, coinciding with a well-established mitochondrial metabolic defect under these conditions. Specifically, we demonstrated that a fragment (named mt-tRF-LeuTAA) resulting from the cleavage of mt-tRNA-LeuTAA, encoded by the mitochondrial genome and found to be reduced in the islets of db/db mice, acts as a key regulator of mitochondrial OXPHOS functions, mitochondrial membrane potential, the insulin secretory capacity of ß-cells, and the insulin sensitivity of myotube muscle cells.

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Project description:Parental dietary conditions can influence the metabolic traits of offspring. In mice, paternal consumption of low protein diet alters cholesterol and lipid metabolism of progeny. Here, we examine RNA species expressed in male reproductive tissues of mice. Protein restriction leads to altered levels of multiple small RNAs in mature sperm, as well as throughout the male reproductive tract, with decreased levels of let-7 family members and increased levels of 5â?? fragments of tRNA-Gly isoacceptors. Intriguingly, tRNA fragments are scarce in the testis, but their levels increase in sperm during posttesticular maturation in the epididymis. We find that epididymosomes â?? extracellular vesicles which fuse with sperm during epididymal transit â?? exhibit RNA payloads closely matching those of mature sperm, and can deliver tRNA fragments to immature sperm in vitro both in mouse and in bull. Finally, we show that tRNA-Gly-GCC fragments play a role in repressing genes associated with the endogenous retroelement MERVL, both in ES cells and in preimplantation embryos. Our results shed light on small RNA biogenesis during post-testicular sperm maturation, and link tRNA fragments to regulation of endogenous retroelements active in the early embryo. E14 mESCs were transfected with LNA-containing oligos antisense to tRF-GG or GFP-esiRNA as control, then either total RNA was isolated or 80S ribosomes were isolated from Rnase-digested whole cell lysate, and footprints between 26-32nt were collected for ribosome profiling library construction using a kit-free protocol based on Heyer et al. 2015 NAR.

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Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals (smallRNA-seq)

Project description:Parental dietary conditions can influence the metabolic traits of offspring. In mice, paternal consumption of low protein diet alters cholesterol and lipid metabolism of progeny. Here, we examine RNA species expressed in male reproductive tissues of mice. Protein restriction leads to altered levels of multiple small RNAs in mature sperm, as well as throughout the male reproductive tract, with decreased levels of let-7 family members and increased levels of 5â fragments of tRNA-Gly isoacceptors. Intriguingly, tRNA fragments are scarce in the testis, but their levels increase in sperm during post-testicular maturation in the epididymis. We find that epididymosomes â extracellular vesicles which fuse with sperm during epididymal transit â exhibit RNA payloads closely matching those of mature sperm, and can deliver tRNA fragments to immature sperm in vitro both in mouse and in bull. Finally, we show that tRNA-Gly-GCC fragments play a role in repressing genes associated with the endogenous retroelement MERVL, both in ES cells and in preimplantation embryos. Our results shed light on small RNA biogenesis during post-testicular sperm maturation, and link tRNA fragments to regulation of endogenous retroelements active in the early embryo. Small RNA (<40nt) profile of various tissues and cells was examined by deep sequencing

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