A transfer-RNA-derived small RNA regulates ribosome biogenesis

Kim, Hak Kyun; Fuchs, Gabriele; Wang, Shengchun; Wei, Wei; Zhang, Yue; Park, Hyesuk; Roy-Chaudhuri, Biswajoy; Li, Pan; Xu, Jianpeng; Chu, Kirk; Zhang, Feijie; Chua, Mei-Sze; So, Samuel; Zhang, Qiangfeng Cliff; Sarnow, Peter; Kay, Mark A.

doi:10.1038/nature25005

Cited by 406 publications

(447 citation statements)

References 47 publications

Supporting

Mentioning

410

Contrasting

Order By: Relevance

“…Based on the region of tRNA from which these small RNAs are processed, these can be classified into five different species: 32-34 nt 5 0 -and 3 0halves; 18-22 nt 5 0 -and 3 0 -tRNA fragments (tRFs); and 3 0 U tRFs [2,3]. There is growing evidence that these small RNAs are involved in regulating several biological processes, such as tumor suppression [7], ribosomal biogenesis in cancer [8], paternal epigenetic inheritance [9,10], and LTR-retrotransposon control [11] through distinct mechanisms. The widespread and conserved expression of these small RNAs across several biological systems has piqued the interest in understanding the functional significance of these tRNAderived small RNAs.…”

Section: Introductionmentioning

confidence: 99%

Dynamic expression of tRNA‐derived small RNAs define cellular states

et al. 2019

View full text Add to dashboard Cite

Transfer RNA (tRNA)‐derived small RNAs (tsRNAs) have recently emerged as important regulators of protein translation and shown to have diverse biological functions. However, the underlying cellular and molecular mechanisms of tsRNA function in the context of dynamic cell‐state transitions remain unclear. Expression analysis of tsRNAs in distinct heterologous cell and tissue models of stem vs. differentiated states revealed a differentiation‐dependent enrichment of 5′‐tsRNAs. We report the identification of a set of 5′‐tsRNAs that is upregulated in differentiating mouse embryonic stem cells (mESCs). Notably, interactome studies with differentially enriched 5′‐tsRNAs revealed a switch in their association with “effector” RNPs and “target” mRNAs in different cell states. We demonstrate that specific 5′‐tsRNAs can preferentially interact with the RNA‐binding protein, Igf2bp1, in the RA‐induced differentiated state. This association influences the transcript stability and thereby translation of the pluripotency‐promoting factor, c‐Myc, thus providing a mechanistic basis for how 5′‐tsRNAs can modulate stem cell states in mESCs. Together our study highlights the role of 5′‐tsRNAs in defining distinct cell states.

show abstract

Section: Introductionmentioning

confidence: 99%

Dynamic expression of tRNA‐derived small RNAs define cellular states

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Several lines of evidence indicate that ncRNA regulate multiple stages of life cycle, including development, differentiation and aging, through the regulation of target gene expression . Broadly, ncRNA can be classified into two groups: small ncRNA 18‐200 nt in length and lncRNA …”

Section: Introductionmentioning

confidence: 99%

Development of miRNA‐based therapeutic approaches for cancer patients

Takahashi

Prieto‐Vila

Kohama³

et al. 2019

Cancer Science

107

View full text Add to dashboard Cite

Over the past few decades, si RNA and mi RNA have attracted a great deal of attention from researchers and clinicians. These molecules have been extensively studied from the standpoint of developing biopharmaceuticals against various diseases, including heart disease, diabetes and cancers. si RNA suppresses only a single target, whereas each mi RNA regulates the expression of multiple target genes. More importantly, because mi RNA are also secreted from cancer cells, and their aberrant expression is associated with tumor development and progression, they represent not only therapeutic targets but also promising biomarkers for diagnosis and prognosis. Therefore, mi RNA may be more effective tools against cancers, in which multiple signal pathways are dysregulated. In this review, we summarize recent progress in the development of mi RNA therapeutics for the treatment of cancer patients, and describe delivery systems for oligonucleotide therapeutics.

show abstract

“…Investigations in D. melanogaster show that some tRNA fragments modulate the translation of mRNA through antisense base‐pairing in a manner that is dependent upon Ago2 , by modulating expression of the translational machinery. Related to this finding, in humans, a tRNA fragment derived from tRNA Leu base‐pairs with RPS28 mRNA and promotes its expression . In this instance, rather than functioning via an Ago‐mediated pathway, the tRF prevents deleterious secondary structure formation in the mRNA.…”

Section: Constitutive Trna Fragmentsmentioning

confidence: 97%

The role of RNA modifications in the regulation of tRNA cleavage

2018

View full text Add to dashboard Cite

Transfer RNA (tRNA) have been harbingers of many paradigms in RNA biology. They are among the first recognized noncoding RNA (ncRNA) playing fundamental roles in RNA metabolism. Although mainly recognized for their role in decoding mRNA and delivering amino acids to the growing polypeptide chain, tRNA also serve as an abundant source of small ncRNA named tRNA fragments. The functional significance of these fragments is only beginning to be uncovered. Early on, tRNA were recognized as heavily post-transcriptionally modified, which aids in proper folding and modulates the tRNA:mRNA anticodon-codon interactions. Emerging data suggest that these modifications play critical roles in the generation and activity of tRNA fragments. Modifications can both protect tRNA from cleavage or promote their cleavage. Modifications to individual fragments may be required for their activity. Recent work has shown that some modifications are critical for stem cell development and that failure to deposit certain modifications has profound effects on disease. This review will discuss how tRNA modifications regulate the generation and activity of tRNA fragments.

show abstract

A transfer-RNA-derived small RNA regulates ribosome biogenesis

Cited by 406 publications

References 47 publications

Dynamic expression of tRNA‐derived small RNAs define cellular states

Dynamic expression of tRNA‐derived small RNAs define cellular states

Development of miRNA‐based therapeutic approaches for cancer patients

The role of RNA modifications in the regulation of tRNA cleavage

Contact Info

Product

Resources

About