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TRNA-derived small RNAs target transposable element transcripts

ABSTRACT: Background: Eukaryotic organisms have evolved a series of mechanisms to regulate transposable element (TE) expression based on RNA silencing. In plants, the initial step in the recognition of TE transcripts relies on microRNAs, but this is unlikely to take place in the pollen grain where natural reactivation of TE transcription occurs but microRNAs accumulate to low levels. We investigated small non-coding RNA accumulation in plants and found conserved tRNA-derived RNA fragment (tRF) accumulation in the pollen grain or analogous reproductive structure in a variety of plant species. Results:Analysis of tRF biology in Arabidopsis revealed that tRFs are regulated by the chromatin modifier DDM1, have a microRNA-like biogenesis pathway, and specifically target TE mRNAs. In addition, we provide evidence that tRF targeting is involved in the production of secondary small RNAs derived from TE transcripts, which initiate a cascade of RNAi and TE silencing. Conclusion:that tRFs are bona-fide regulatory microRNA-like small RNAs involved in the regulation of genome stability through the targeting of TE transcripts.

ORGANISM(S): Arabidopsis thaliana

PROVIDER: GSE63879 | GEO | 2017/02/23

SECONDARY ACCESSION(S): PRJNA269310

REPOSITORIES: GEO

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Project description:Background: As couples struggle with infertility and livestock producers wish to rapidly improve genetic merit in their herd, assisted reproductive technologies (ART) have become increasingly popular in human medicine as well as the livestock industry. Utilizing ART can cause an increased risk of congenital overgrowth syndromes, such as Large Offspring Syndrome (LOS) in ruminants. A dysregulation of transcripts has been observed in bovine fetuses with LOS, which is suggested to be a cause of the phenotype. Our recent study identified variations in tRNA expression in LOS individuals, leading us to hypothesize that variations in tRNA expression can influence the availability of their processed regulatory products, tRNA-derived fragments (tRFs). Due to their resemblance in size to microRNAs, studies suggest that tRFs target mRNA transcripts and regulate gene expression. Thus, we have sequenced small RNA isolated from skeletal muscle and liver of day 105 bovine fetuses to elucidate the mechanisms contributing to LOS. Moreover, we have utilized our previously generated tRNA sequencing data to analyze the contribution of tRNA availability to tRF abundance. Results: 22,289 and 7,737 unique tRFs were predicted in the liver and muscle tissue respectively. The greatest number of reads originated from 5′ tRFs in muscle and 5′ halves in liver. In addition, mitochondrial (MT) and nuclear derived tRF expression was tissue-specific with most MT-tRFs and nuclear tRFs derived from LysUUU and iMetCAU in muscle, and AsnGUU and GlyGCC in liver. Despite variation in tRF abundance within treatment groups, we identified differentially expressed (DE) tRFs across Control-AI, ART-Normal, and ART-LOS groups with the most DE tRFs between ART-Normal and ART-LOS groups. Many DE tRFs target transcripts enriched in pathways related to growth and development in the muscle and tumor development in the liver. Finally, we found positive correlation coefficients between tRNA availability and tRF expression in muscle (R = 0.47) and liver (0.6). Conclusion: Our results highlight the dysregulation of tRF expression and its regulatory roles in LOS. These tRFs were found to target both imprinted and non-imprinted genes in muscle as well as genes linked to tumor development in the liver. Furthermore, we found that tRNA transcription is a highly modulated event that plays a part in the biogenesis of tRFs. This study is the first to investigate the relationship between tRNA and tRF expression in combination with ART-induced LOS.

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TRNA-derived small RNAs target transposable element transcripts

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