5â€² tRNA Halves: The Next Generation of Immune Signaling Molecules

Dhahbi, Joseph M.

doi:10.3389/fimmu.2015.00074

Cited by 75 publications

(73 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently tRNA fragments (tRF) have also been shown to be present in extracellular RNA in biofluids151719. Mature tRNAs contain a number of post transcriptional modifications which hinder efficient sequencing by NGS2728.…”

Section: Resultsmentioning

confidence: 99%

Total Extracellular Small RNA Profiles from Plasma, Saliva, and Urine of Healthy Subjects

Yeri

Courtright

Reiman

et al. 2017

Sci Rep

145

151

View full text Add to dashboard Cite

Interest in circulating RNAs for monitoring and diagnosing human health has grown significantly. There are few datasets describing baseline expression levels for total cell-free circulating RNA from healthy control subjects. In this study, total extracellular RNA (exRNA) was isolated and sequenced from 183 plasma samples, 204 urine samples and 46 saliva samples from 55 male college athletes ages 18–25 years. Many participants provided more than one sample, allowing us to investigate variability in an individual’s exRNA expression levels over time. Here we provide a systematic analysis of small exRNAs present in each biofluid, as well as an analysis of exogenous RNAs. The small RNA profile of each biofluid is distinct. We find that a large number of RNA fragments in plasma (63%) and urine (54%) have sequences that are assigned to YRNA and tRNA fragments respectively. Surprisingly, while many miRNAs can be detected, there are few miRNAs that are consistently detected in all samples from a single biofluid, and profiles of miRNA are different for each biofluid. Not unexpectedly, saliva samples have high levels of exogenous sequence that can be traced to bacteria. These data significantly contribute to the current number of sequenced exRNA samples from normal healthy individuals.

show abstract

Section: Resultsmentioning

confidence: 99%

Total Extracellular Small RNA Profiles from Plasma, Saliva, and Urine of Healthy Subjects

Yeri

Courtright

Reiman

et al. 2017

Sci Rep

145

151

View full text Add to dashboard Cite

show abstract

“…Once thought to be noncatalytic messengers and scaffolds for use in translation, RNA has been shown to play active roles in such diverse processes as mRNA splicing (Kruger et al 1982;McNeil et al 2016), regulation of transcription (Grundy et al 1994;Henkin 1994;Serganov and Nudler 2013;Furtig et al 2015) and translation (Lee et al 1993;Wightman et al 1993;Filipowicz et al 2008), viral assembly (Zeffman et al 2000;Cantara et al 2014;Sardo et al 2015;Stockley et al 2016), and immunity (Brouns et al 2008;Zhang et al 2010;Dhahbi 2015;Cavalieri et al 2016). Many of these functions result from the ability of RNA to fold into complex secondary and tertiary structures.…”

Section: Introductionmentioning

confidence: 99%

RiboCAT: a new capillary electrophoresis data analysis tool for nucleic acid probing

Cantara

Hatterschide

et al. 2016

RNA

View full text Add to dashboard Cite

Chemical and enzymatic probing of RNA secondary structure and RNA/protein interactions provides the basis for understanding the functions of structured RNAs. However, the ability to rapidly perform such experiments using capillary electrophoresis has been hampered by relatively labor-intensive data analysis software. While these computationally robust programs have been shown to calculate residue-specific reactivities to a high degree of accuracy, they often require time-consuming manual intervention and lack the ability to be easily modified by users. To alleviate these issues, RiboCAT (Ribonucleic acid capillaryelectrophoresis analysis tool) was developed as a user-friendly, Microsoft Excel-based tool that reduces the need for manual intervention, thereby significantly shortening the time required for data analysis. Features of this tool include (i) the use of an Excel platform, (ii) a method of intercapillary signal alignment using internal size standards, (iii) a peak-sharpening algorithm to more accurately identify peaks, and (iv) an open architecture allowing for simple user intervention. Furthermore, a complementary tool, RiboDOG (RiboCAT data output generator) was designed to facilitate the comparison of multiple data sets, highlighting potential inconsistencies and inaccuracies that may have occurred during analysis. Using these new tools, the secondary structure of the HIV-1 5 ′ untranslated region (5 ′ UTR) was determined using selective 2 ′ -hydroxyl acylation analyzed by primer extension (SHAPE), matching the results of previous work.

show abstract

“…tRNA halves have been shown to play diverse roles in different aspects of biology [26,27]. In particular, tRNA halves can be generated in response to diverse stimuli including viral infection and sex hormone [42,53,54,63] and have been proposed to be new signaling molecules in immune biology [46]. Moreover, tRNA halves were found abundantly in body fluids, including blood/serum, sperm, cerebrospinal fluid and more [63][64][65][66][67][68][69][70].…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, tRFs are a newly identified class of non-coding RNAs that are beginning to be linked to various biological functions, including the regulation of gene expression and epigenetics [19,[26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45]. A group of tRFs, tRNA halves, generated by cleavage at tRNA anticodon loop, can be induced by different forms of stress including viral infection and RNases in innate immune responses [46][47][48][49][50][51][52][53][54][55]. Yet how environmental risk factors that have been linked to ASD, such as MIA, affect miR and tRF expression during fetal development has not been extensively studied.…”

Section: Introductionmentioning

confidence: 99%

tRNA-derived fragments and microRNAs in the maternal-fetal interface of a mouse maternal-immune-activation autism model

Frost

Lammert

et al. 2019

Preprint

View full text Add to dashboard Cite

tRNA-derived small fragments (tRFs) and tRNA halves have emerging functions in different biological pathways, such as regulating gene expression, protein translation, retrotransposon activity, transgenerational epigenetic changes and response to environmental stress. However, small RNAs like tRFs and microRNAs in the maternal-fetal interface during gestation have not been studied extensively. Here we investigated the small RNA composition of mouse placenta/decidua, which represents the interface where the mother communicates with the fetus, to determine whether there are specific differences in tRFs and microRNAs during fetal development and in response to maternal immune activation (MIA). Global tRF expression pattern, just like microRNAs, can distinguish tissue types among placenta/decidua, fetal brain and fetal liver. In particular, 5' tRNA halves from tRNA Gly , tRNA Glu , tRNA Val and tRNA Lys are abundantly expressed in the normal mouse placenta/decidua. Moreover, tRF and microRNA levels in the maternal-fetal-interface change dynamically over the course of embryonic development. To see if stress alters non-coding RNA expression at the maternal-fetal interface, we treated pregnant mice with a viral infection mimetic, which has been shown to promote autism-related phenotypes in the offspring. Acute changes in the levels of specific tRFs and microRNAs were observed 3-6 hours after MIA and are suppressed thereafter. A group of 5' tRNA halves is down-regulated by MIA, whereas a group of 18-nucleotide tRF-3a is up-regulated. In conclusion, tRFs show tissue-specificity, developmental changes and acute response to environmental stress, opening the possibility of them having a role in the fetal response to MIA.

show abstract

5â€² tRNA Halves: The Next Generation of Immune Signaling Molecules

Cited by 75 publications

References 49 publications

Total Extracellular Small RNA Profiles from Plasma, Saliva, and Urine of Healthy Subjects

Total Extracellular Small RNA Profiles from Plasma, Saliva, and Urine of Healthy Subjects

RiboCAT: a new capillary electrophoresis data analysis tool for nucleic acid probing

tRNA-derived fragments and microRNAs in the maternal-fetal interface of a mouse maternal-immune-activation autism model

Contact Info

Product

Resources

About