A transfer-RNA-derived small RNA regulates ribosome biogenesis
Hak Kyun Kim,Gabriele Fuchs,Shengchun Wang,Wei Wei,Yue Zhang,Hyesuk Park,Biswajoy Roy-Chaudhuri,Pan Li,Jianpeng Xu,Kirk Chu,Feijie Zhang,Mei-Sze Chua,Samuel So,Qiangfeng Cliff Zhang,Peter Sarnow,Mark A. Kay +15 more
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TLDR
In conclusion, inhibition of a specific tsRNA, LeuCAG3′tsRNA, induces apoptosis in rapidly dividing cells in vitro and in a patient-derived orthotopic hepatocellular carcinoma model in mice, establishing a post-transcriptional mechanism that can fine-tune gene expression during different physiological states and provide a potential new target for treating cancer.Abstract:
Transfer-RNA-derived small RNAs (tsRNAs; also called tRNA-derived fragments) are an abundant class of small non-coding RNAs whose biological roles are not well understood. Here we show that inhibition of a specific tsRNA, LeuCAG3′tsRNA, induces apoptosis in rapidly dividing cells in vitro and in a patient-derived orthotopic hepatocellular carcinoma model in mice. This tsRNA binds at least two ribosomal protein mRNAs (RPS28 and RPS15) to enhance their translation. A decrease in translation of RPS28 mRNA blocks pre-18S ribosomal RNA processing, resulting in a reduction in the number of 40S ribosomal subunits. These data establish a post-transcriptional mechanism that can fine-tune gene expression during different physiological states and provide a potential new target for treating cancer. A 22-nucleotide fragment of a transfer RNA regulates translation by binding to the mRNA of a ribosomal protein and increasing its expression, and downregulation of the fragment in patient-derived liver tumour cells reduces tumour growth in mice. The functional roles of small RNA fragments derived from tRNAs are not well known, but evidence is growing that some play a part in various cellular processes. Mark Kay and colleagues show that a 22-nucleotide fragment from the 3′ end of leucine tRNA can regulate translation. The fragment binds to the mRNA of a ribosomal protein to upregulate its expression. When this interaction is suppressed in human cells in culture, cell death occurs. Decreasing the levels of the tRNA fragment with an antisense oligonucleotide can slow the growth of liver tumours in mice. Technologies aimed at reducing expression of this tRNA fragment might have utility in treating cancer.read more
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The Role of Non-coding RNAs in Oncology
TL;DR: For decades, research into cancer biology focused on the involvement of protein-coding genes, but an explosion of studies into ncRNA biology has shown that they represent a diverse and prevalent group of RNAs, including both oncogenic molecules and those that work in a tumor suppressive manner.
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Dnmt2 mediates intergenerational transmission of paternally acquired metabolic disorders through sperm small non-coding RNAs.
Yunfang Zhang,Yunfang Zhang,Xudong Zhang,Junchao Shi,Francesca Tuorto,Xin Li,Yusheng Liu,Reinhard Liebers,Liwen Zhang,Yongcun Qu,Jingjing Qian,Maya Pahima,Ying Liu,Menghong Yan,Zhonghong Cao,Zhonghong Cao,Xiaohua Lei,Yujing Cao,Hongying Peng,Shichao Liu,Yue Wang,Huili Zheng,Rebekah Woolsey,David R. Quilici,Qiwei Zhai,Lei Li,Tong Zhou,Wei Yan,Frank Lyko,Ying Zhang,Qi Zhou,Enkui Duan,Qi Chen +32 more
TL;DR: It is reported that tRNA methyltransferase Dnmt2 is required for sperm small-non-coding-RNA-mediated transmission of paternal metabolic disorders to the offspring and that DnMT2-mediated m5C contributes to the secondary structure and biological properties of sncRNAs, implicating sperm RNA modifications as an additional layer of paternal hereditary information.
Journal ArticleDOI
tRNA fragments (tRFs) guide Ago to regulate gene expression post-transcriptionally in a Dicer-independent manner.
TL;DR: It is shown that endogenous 18 nucleotide tRFs derived from the 3' ends of tRNAs (tRF-3) post-transcriptionally repress genes in HEK293T cells in culture and RNA-seq demonstrates that endogenous target genes are specifically decreased upon t RF-3 induction.
Journal ArticleDOI
tRNA-Derived Small RNA: A Novel Regulatory Small Non-Coding RNA
TL;DR: The biogeneses of various tsRNAs are summarized, the emerging concepts regarding functions and mechanisms of action are presented, the potential application of ts RNAs in human diseases is highlighted, and the current problems and future research directions are put forward.
Journal ArticleDOI
Exosomal tRNA-derived small RNA as a promising biomarker for cancer diagnosis
Lei Zhu,Jiao Li,Youling Gong,Qingbin Wu,Shuangyan Tan,Dan Sun,Xiaomin Xu,Yuanli Zuo,Yun Zhao,Yuquan Wei,Xiawei Wei,Yong Peng +11 more
TL;DR: Exosomal tsRNA levels between liver cancer patients and healthy donors are compared, and it is revealed that tsRNAs were dramatically increased in plasma exosomes of Liver cancer patients, demonstrating that plasmaExosome tsRNA could serve as a novel diagnostic biomarker for cancer diagnosis.
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