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Alan Van Goethem, Nurten Yigit, Celine Everaert, Myrthala Moreno-Smith, Liselot M Mus, Eveline Barbieri, Frank Speleman, Pieter Mestdagh, Jason Shohet, Tom Van Maerken, Jo Vandesompele
The ongoing ascent of sequencing technologies has enabled researchers to gain unprecedented insights into the RNA content of biological samples. MiRNAs, a class of small non-coding RNAs, play a pivotal role in regulating gene expression. The discovery that miRNAs are stably present in circulation has spiked interest in their potential use as minimally-invasive biomarkers. However, sequencing of blood-derived samples (serum, plasma) is challenging due to the often low RNA concentration, poor RNA quality and the presence of highly abundant RNAs that dominate sequencing libraries...
November 30, 2016: Scientific Reports
I-Fang Chung, Shing-Jyh Chang, Chen-Yang Chen, Shu-Hsuan Liu, Chia-Yang Li, Chia-Hao Chan, Chuan-Chi Shih, Wei-Chung Cheng
We previously presented the YM500 database, which contains >8000 small RNA sequencing (smRNA-seq) data sets and integrated analysis results for various cancer miRNome studies. In the updated YM500v3 database ( presented herein, we not only focus on miRNAs but also on other functional small non-coding RNAs (sncRNAs), such as PIWI-interacting RNAs (piRNAs), tRNA-derived fragments (tRFs), small nuclear RNAs (snRNAs) and small nucleolar RNAs (snoRNAs). There is growing knowledge of the role of sncRNAs in gene regulation and tumorigenesis...
November 29, 2016: Nucleic Acids Research
Valérie Cognat, Geoffrey Morelle, Cyrille Megel, Stéphanie Lalande, Jean Molinier, Timothée Vincent, Ian Small, Anne-Marie Duchêne, Laurence Maréchal-Drouard
In the expanding repertoire of small noncoding RNAs (ncRNAs), tRNA-derived RNA fragments (tRFs) have been identified in all domains of life. Their existence in plants has been already proven but no detailed analysis has been performed. Here, short tRFs of 19-26 nucleotides were retrieved from Arabidopsis thaliana small RNA libraries obtained from various tissues, plants submitted to abiotic stress or fractions immunoprecipitated with ARGONAUTE 1 (AGO1). Large differences in the tRF populations of each extract were observed...
November 28, 2016: Nucleic Acids Research
Jennifer Gebetsberger, Leander Wyss, Anna M Mleczko, Julia Reuther, Norbert Polacek
Posttranscriptional processing of RNA molecules is a common strategy to enlarge the structural and functional repertoire of RNomes observed in all three domains of life. Fragmentation of RNA molecules of basically all functional classes has been reported to yield smaller non-protein coding RNAs (ncRNAs) that typically possess different roles compared to their parental transcripts. Here we show that a valine tRNA-derived fragment (Val-tRF) that is produced under certain stress conditions in the halophilic archaeon Haloferax volcanii is capable of binding to the small ribosomal subunit...
November 28, 2016: RNA Biology
Theodoros Eleftheriadis, Georgios Pissas, Maria Sounidaki, Nikolaos Antoniadis, Georgia Antoniadi, Vassilios Liakopoulos, Ioannis Stefanidis
Under growth conditions, angiogenin is translocated into the nucleus, where it enhances ribosomal RNA transcription, facilitating increased protein synthesis and cellular proliferation. During stress conditions, angiogenin is sequestered in the cytoplasm, where it cleaves transfer RNA (tRNA) to produce tRNA-derived, stress-induced small RNAs (tiRNAs) that inhibit global protein synthesis, but increase the translation of anti-apoptotic factors. In the present study, the role of angiogenin in the human alloreactive immune response was evaluated using mixed lymphocyte reactions (MLRs) and neamine, an inhibitor of angiogenin nuclear translocation...
November 2016: Experimental and Therapeutic Medicine
Megumi Shigematsu, Yohei Kirino
Transfer RNAs (tRNAs) are fundamental adapter components of translational machinery. tRNAs can further serve as a source of tRNA-derived non-coding RNAs that play important roles in various biological processes beyond translation. Among all species of tRNAs, tRNAHisGUG has been known to uniquely contain an additional guanosine residue at the -1 position (G-1) of its 5'-end. To analyze this -1 nucleotide in detail, we developed a TaqMan qRT-PCR method which can distinctively quantify human mature cytoplasmic tRNAHisGUG containing G-1, U-1, A-1, or C-1 or lacking the -1 nucleotide (starting from G1)...
November 22, 2016: RNA
David Lalaouna, Karine Prévost, Alex Eyraud, Eric Massé
Recent advances in high-throughput sequencing have led to an explosion in the rate of small regulatory RNAs (sRNAs) discovery among bacteria. However, only a handful of them are functionally characterized. Most of the time, little to no targets are known. In Lalaouna et al. (2015), we proposed a new technology to uncover sRNAs targetome, which is based on the MS2-affinity purification (MAPS). We were able to prove its efficiency by applying it on well-characterized sRNAs of Escherichia coli. Thereafter, we adapted the procedure to other kind of RNA (mRNAs and tRNA-derived RNA fragments) and bacteria (pathogenic or Gram-positive strains)...
November 19, 2016: Methods: a Companion to Methods in Enzymology
Cristiane S Alves, Renato Vicentini, Gustavo T Duarte, Vitor F Pinoti, Michel Vincentz, Fabio T S Nogueira
The manuscript by Alves et al. entitled "Genome-wide identification and characterization of tRNA-derived RNA fragments in land plants" describes the identification and characterization of tRNAderived sRNA fragments in plants. By combining bioinformatic analysis and genetic and molecular approaches, we show that tRF biogenesis does not rely on canonical microRNA/siRNA processing machinery (i.e., independent of DICER-LIKE proteins). Moreover, we provide evidences that the Arabidopsis S-like Ribonuclease 1 (RNS1) might be involved in the biogenesis of tRFs...
September 28, 2016: Plant Molecular Biology
Kamilla Bąkowska-Żywicka, Marta Kasprzyk, Tomasz Twardowski
Recently, a number of ribosome-associated non-coding RNAs (rancRNAs) have been discovered in all three domains of life. In our previous studies, we have described several types of rancRNAs in Saccharomyces cerevisiae, derived from many cellular RNAs, including mRNAs, rRNAs, tRNAs and snoRNAs. Here, we present the evidence that the tRNA fragments from simple eukaryotic organism S. cerevisiae directly bind to the ribosomes. Interestingly, rancRNA-tRFs in yeast are derived from both, 5'- and 3'-part of the tRNAs and both types of tRFs associate with the ribosomes in vitro The location of tRFs within the ribosomes is distinct from classical A- and P-tRNA binding sites...
September 2016: FEMS Yeast Research
Kevin A Goncalves, Lev Silberstein, Shuping Li, Nicolas Severe, Miaofen G Hu, Hailing Yang, David T Scadden, Guo-Fu Hu
Regulation of stem and progenitor cell populations is critical in the development, maintenance, and regeneration of tissues. Here, we define a novel mechanism by which a niche-secreted RNase, angiogenin (ANG), distinctively alters the functional characteristics of primitive hematopoietic stem/progenitor cells (HSPCs) compared with lineage-committed myeloid-restricted progenitor (MyePro) cells. Specifically, ANG reduces the proliferative capacity of HSPC while simultaneously increasing proliferation of MyePro cells...
August 11, 2016: Cell
Dario Veneziano, Sebastiano Di Bella, Giovanni Nigita, Alessandro Laganà, Afredo Ferro, Carlo M Croce
One of the most significant biological discoveries of the last decade is represented by the reality that the vast majority of the transcribed genomic output comprises diverse classes of noncoding RNAs (ncRNAs) that may play key roles and/or be affected by many biochemical cellular processes (i.e., RNA editing), with implications in human health and disease. With 90% of the human genome being transcribed and novel classes of ncRNA emerging (tRNA-derived small RNAs and circular RNAs among others), the great majority of the human transcriptome suggests that many important ncRNA functions/processes are yet to be discovered...
December 2016: Human Mutation
Andrew Schuster, Michael K Skinner, Wei Yan
Exposure to the agricultural fungicide vinclozolin during gestation promotes a higher incidence of various diseases in the subsequent unexposed F3 and F4 generations. This phenomenon is termed epigenetic transgenerational inheritance and has been shown to in part involve alterations in DNA methylation, but the role of other epigenetic mechanisms remains unknown. The current study investigated the alterations in small noncoding RNA (sncRNA) in the sperm from F3 generation control and vinclozolin lineage rats...
2016: Environmental Epigenetics
Menghong Yan, Qiwei Zhai
Many findings support the hypothesis that metabolic changes associated with environmental factors can be transmitted from father to offspring. The molecular mechanisms underlying the intergenerational transmission of metabolic changes remain to be fully explored. These acquired metabolic disorders in offspring may be partially explained by some potential epigenetic information carriers such as DNA methylation, histone modification and small non-coding RNAs. Recent evidence shows that sperm tRNA-derived small RNAs (tsRNAs) as a type of paternal epigenetic information carrier may mediate intergenerational inheritance...
September 2016: Journal of Endocrinology
Srinivasan Asha, Eppurath V Soniya
Small RNAs derived from transfer RNAs were recently assigned as potential gene regulatory candidates for various stress responses in eukaryotes. In this study, we report on the cloning and identification of tRNA derived small RNAs from black pepper plants in response to the infection of the quick wilt pathogen, Phytophthora capsici. 5'tRFs cloned from black pepper were validated as highly expressed during P. capsici infection. A high-throughput systematic analysis of the small RNAome (sRNAome) revealed the predominance of 5'tRFs in the infected leaf and root...
2016: Frontiers in Plant Science
Ken Ikeuchi, Toshifumi Inada
Dom34-Hbs1 stimulates degradation of aberrant mRNAs lacking termination codons by dissociating ribosomes stalled at the 3' ends, and plays crucial roles in Nonstop Decay (NSD) and No-Go Decay (NGD). In the dom34Δ mutant, nonstop mRNA is degraded by sequential endonucleolytic cleavages induced by a stalled ribosome at the 3' end. Here, we report that ribosome-associated Asc1/RACK1 is required for the endonucleolytic cleavage of nonstop mRNA by stalled ribosome at the 3' end of mRNA in dom34Δ mutant cells. Asc1/RACK1 facilitates degradation of truncated GFP-Rz mRNA in the absence of Dom34 and exosome-dependent decay...
2016: Scientific Reports
Shozo Honda, Yohei Kirino
Sex hormones and their receptors play critical roles in the genesis and progression of breast and prostate cancers. We recently discovered that sex hormone signaling pathways promote the expression of specific tRNA halves termed Sex HOrmone-dependent TRNA-derived RNAs (SHOT-RNAs). Functional involvement of SHOT-RNAs in cell proliferation suggests a novel tRNA-engaged pathway in tumorigenesis.
March 2016: Molecular & Cellular Oncology
Jin Liu, Luyao Shao, Phong Trang, Zhu Yang, Michael Reeves, Xu Sun, Gia-Phong Vu, Yu Wang, Hongjian Li, Congyi Zheng, Sangwei Lu, Fenyong Liu
An external guide sequence (EGS) is a RNA sequence which can interact with a target mRNA to form a tertiary structure like a pre-tRNA and recruit intracellular ribonuclease P (RNase P), a tRNA processing enzyme, to degrade target mRNA. Previously, an in vitro selection procedure has been used by us to engineer new EGSs that are more robust in inducing human RNase P to cleave their targeted mRNAs. In this study, we constructed EGSs from a variant to target the mRNA encoding herpes simplex virus 1 (HSV-1) major transcription regulator ICP4, which is essential for the expression of viral early and late genes and viral growth...
June 9, 2016: Scientific Reports
Wenna Zhang, Christoph J Thieme, Gregor Kollwig, Federico Apelt, Lei Yang, Nikola Winter, Nadine Andresen, Dirk Walther, Friedrich Kragler
In plants, protein-coding mRNAs can move via the phloem vasculature to distant tissues, where they may act as non-cell-autonomous signals. Emerging work has identified many phloem-mobile mRNAs, but little is known regarding RNA motifs triggering mobility, the extent of mRNA transport, and the potential of transported mRNAs to be translated into functional proteins after transport. To address these aspects, we produced reporter transcripts harboring tRNA-like structures (TLSs) that were found to be enriched in the phloem stream and in mRNAs moving over chimeric graft junctions...
June 2016: Plant Cell
Ling-Ling Zheng, Wei-Lin Xu, Shun Liu, Wen-Ju Sun, Jun-Hao Li, Jie Wu, Jian-Hua Yang, Liang-Hu Qu
tRNA-derived small RNA fragments (tRFs) are one class of small non-coding RNAs derived from transfer RNAs (tRNAs). tRFs play important roles in cellular processes and are involved in multiple cancers. High-throughput small RNA (sRNA) sequencing experiments can detect all the cellular expressed sRNAs, including tRFs. However, distinguishing genuine tRFs from RNA fragments generated by random degradation remains a major challenge. In this study, we developed an integrated web-based computing system, tRF2Cancer, to accurately identify tRFs from sRNA deep-sequencing data and evaluate their expression in multiple cancers...
July 8, 2016: Nucleic Acids Research
Shawn M Lyons, Chris Achorn, Nancy L Kedersha, Paul J Anderson, Pavel Ivanov
Stress-induced angiogenin (ANG)-mediated tRNA cleavage promotes a cascade of cellular events that starts with production of tRNA-derived stress-induced RNAs (tiRNAs) and culminates with enhanced cell survival. This stress response program relies on a subset tiRNAs that inhibit translation initiation and induce the assembly of stress granules (SGs), cytoplasmic ribonucleoprotein complexes with cytoprotective and pro-survival properties. SG-promoting tiRNAs bear oligoguanine motifs at their 5'-ends, assemble G-quadruplex-like structures and interact with the translational silencer YB-1...
August 19, 2016: Nucleic Acids Research
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