Transfer RNA-Derived Small RNAs: Another Layer of Gene Regulation and Novel Targets for Disease Therapeutics

Kim, Hak Kyun; Yeom, Ji-Hyun; Kay, Mark A.

doi:10.1016/j.ymthe.2020.09.013

Cited by 69 publications

(70 citation statements)

References 124 publications

(197 reference statements)

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“…However, our analysis strongly suggests that the genomic copies of tRNAs are not redundant, but useful as the source of tRFs in the aging process. Although a direct association between tRFs and human aging has not been reported yet, tRFs have been shown to be associated with age-related human diseases, such as cancers and neurodegenerative diseases 21 . Particularly, accumulation of tRFs is observed not only in cells, but also in extracellular environments 22 , suggesting potential of tRFs as promising diagnostic markers 22 .…”

Section: Discussionmentioning

confidence: 99%

“…The number of studies reporting biological activities of tRFs is growing, but all of these studies suffered from frequent nucleotide modification and sequence homology among different tRNA species and isoforms 21 . When analyzing small RNA sequencing data, these characteristics should be considered for the quantification of individual tRFs.…”

Section: Discussionmentioning

confidence: 99%

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Transfer RNA-derived fragments in aging Caenorhabditis elegans originate from abundant homologous gene copies

Shin

Koo

Seo

et al. 2021

Sci Rep

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Small RNAs that originate from transfer RNA (tRNA) species, tRNA-derived fragments (tRFs), play diverse biological functions but little is known for their association with aging. Moreover, biochemical aspects of tRNAs limit discovery of functional tRFs by high throughput sequencing. In particular, genes encoding tRNAs exist as multiple copies throughout genome, and mature tRNAs have various modified bases, contributing to ambiguities for RNA sequencing-based analysis of tRFs. Here, we report age-dependent changes of tRFs in Caenorhabditis elegans. We first analyzed published RNA sequencing data by using a new strategy for tRNA-associated sequencing reads. Our current method used unique mature tRNAs as a reference for the sequence alignment, and properly filtered out false positive enrichment for tRFs. Our analysis successfully distinguished de novo mutation sites from differences among homologous copies, and identified potential RNA modification sites. Overall, the majority of tRFs were upregulated during aging and originated from 5′-ends, which we validated by using Northern blot analysis. Importantly, we revealed that the major source of tRFs upregulated during aging was the tRNAs with abundant gene copy numbers. Our analysis suggests that tRFs are useful biomarkers of aging particularly when they originate from abundant homologous gene copies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Transfer RNA-derived fragments in aging Caenorhabditis elegans originate from abundant homologous gene copies

Shin

Koo

Seo

et al. 2021

Sci Rep

View full text Add to dashboard Cite

show abstract

“…However, our analysis strongly suggests that the genomic copies of tRNAs are not redundant, but useful as the source of tRFs in the aging process. Although a direct association between tRFs and human aging has not been reported yet, tRFs have been shown to be associated with agerelated human diseases, such as cancers and neurodegenerative diseases (21). Particularly, accumulation of tRFs is observed not only in cells, but also in extracellular environments (22), suggesting potential of tRFs as promising diagnostic markers (22).…”

Section: Discussionmentioning

confidence: 99%

Transfer RNA-derived Fragments in Aging Caenorhabditis Elegans Originate from Abundant Homologous Gene Copies

Shin

Koo

Seo

et al. 2021

Preprint

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Small RNAs that originate from transfer RNA (tRNA) species, tRNA-derived fragments (tRFs), play diverse biological functions but little is known for their association with aging. Moreover, biochemical aspects of tRNAs limit discovery of functional tRFs by high throughput sequencing. In particular, genes encoding tRNAs exist as multiple copies throughout genome, and mature tRNAs have various modified bases, contributing to ambiguities for RNA sequencing-based analysis of tRFs. Here, we report age-dependent changes in tRFs that may have functional impacts on aging in Caenorhabditis elegans. We first analyzed published RNA sequencing data by using a new strategy for tRNA-associated sequencing reads. Our current method used unique mature tRNAs as a reference for the sequence alignment, and properly filtered out false positive enrichment for tRFs. Our analysis successfully distinguished de novo mutation sites from differences among homologous copies, and identified potential RNA modification sites. Importantly, we revealed that the major source of tRFs up-regulated during aging was the tRNAs with abundant gene copy numbers. Together, our work raises the possibility that age-dependent changes in tRF levels have functional roles in the lifespan of animals, including C. elegans.

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“…Cell-free DNA is believed to be fragmented and shorter in diseased individuals compared to healthy 3 . In addition to DNA, body fluids contain long non-coding RNAs 11 , tRNA derived fragments 12 , and other RNA oligos in the range of 20 to 300 nucleotides (nt). Among them is a group of single-stranded (ss) RNAs, 17 to 25nt long, microRNAs or miRNAs [13][14][15] .…”

Section: Introductionmentioning

confidence: 99%

Ready-to-use nanopore platform for the detection of any DNA/RNA oligo at attomole range using an Osmium tagged complementary probe

Kang

Bernasconi

Jack

et al. 2020

Preprint

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Nanopores can serve as single molecule sensors. We exploited the MinION, a portable nanopore device from Oxford Nanopore Technologies (ONT), and repurposed it to detect any DNA/RNA oligo (target) in a complex mixture by conducting voltage-driven ion-channel measurements. The detection and quantitation of the target is enabled by the use of a unique complementary probe. Using a validated labeling technology, probes are tagged with a bulky Osmium tag (Osmium tetroxide 2,2’-bipyridine), in a way that preserves strong hybridization between probe and target. Intact oligos traverse the MinION’s nanopore relatively quickly compared to the device’s acquisition rate, and exhibit count of events comparable to the baseline. Counts are reported by a publicly available software, OsBp_detect. Due to the presence of the bulky Osmium tag, probes traverse more slowly, produce multiple counts over the baseline, and are even detected at single digit attomole (amole) range. In the presence of the target the probe is “silenced”. Silencing is attributed to a 1:1 double stranded (ds) complex that doesn’t fit and can’t traverse this nanopore. This ready-to-use platform can be tailored as a diagnostic test to meet the requirements for point-of-care cell-free tumor DNA (ctDNA) and microRNA (miRNA) detection and quantitation in body fluids.

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Transfer RNA-Derived Small RNAs: Another Layer of Gene Regulation and Novel Targets for Disease Therapeutics

Cited by 69 publications

References 124 publications

Transfer RNA-derived fragments in aging Caenorhabditis elegans originate from abundant homologous gene copies

Transfer RNA-derived fragments in aging Caenorhabditis elegans originate from abundant homologous gene copies

Transfer RNA-derived Fragments in Aging Caenorhabditis Elegans Originate from Abundant Homologous Gene Copies

Ready-to-use nanopore platform for the detection of any DNA/RNA oligo at attomole range using an Osmium tagged complementary probe

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