Regulatory RNAs derived from transfer RNA?

Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
RNA (Impact Factor: 4.94). 10/2010; 16(10):1865-9. DOI: 10.1261/rna.2266510
Source: PubMed


Four recent studies suggest that cleavages of transfer RNAs generate products with microRNA-like features, with some evidence of function. If their regulatory functions were to be confirmed, these newly revealed RNAs would add to the expanding repertoire of small noncoding RNAs and would also provide new perspectives on the coevolution of transfer RNA and messenger RNA.

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    • "Our deep sequencing studies of serum/plasma have consistently detected tRNA-derived RNAs of size 30–33 nt (Dhahbi et al., 2013a,b). Intracellular tRNA-derived small RNAs are classified into two types based on their size (Sobala & Hutvagner, 2011; Martens-Uzunova et al., 2013): tRNA halves with size of 30–40 nt produced by cleavage of mature tRNAs, and shorter tRNA-derived fragments (tRFs) of size 18–22 nt produced from both mature and pre-tRNAs by Dicer or RNase Z (Thompson et al., 2008; Cole et al., 2009; Fu et al., 2009; Lee et al., 2009; Thompson & Parker, 2009a; Pederson, 2010; Sobala & Hutvagner, 2011). The tRNA halves class includes 5 0 -and 3 0 -tRNA halves that were first observed in stressed cultured cells where they are produced by cleavage of tRNAs near or at the anticodon loop with the ribonuclease Rny1 in Saccharomyces cerevisiae (Thompson & Parker, 2009b) and Angiogenin in higher eukaryotes (Fu et al., 2009; Yamasaki et al., 2009). "
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    ABSTRACT: Recent evidence demonstrates that serum levels of specific miRNAs significantly change with age. The ability of circulating sncRNAs to act as signaling molecules and regulate a broad spectrum of cellular functions implicates them as key players in the aging process. To discover circulating sncRNAs that impact aging in the long-lived Ames dwarf mice, we conducted deep sequencing of small RNAs extracted from serum of young and old mice. Our analysis showed genotype-specific changes in the circulating levels of 21 miRNAs during aging [genotype-by-age interaction (GbA)]. Genotype-by-age miRNAs showed four distinct expression patterns and significant overtargeting of transcripts involved in age-related processes. Functional enrichment analysis of putative and validated miRNA targets highlighted cellular processes such as tumor suppression, anti-inflammatory response, and modulation of Wnt, insulin, mTOR, and MAPK signaling pathways, among others. The comparative analysis of circulating GbA miRNAs in Ames mice with circulating miRNAs modulated by calorie restriction (CR) in another long-lived mouse suggests CR-like and CR-independent mechanisms contributing to longevity in the Ames mouse. In conclusion, we showed for the first time a signature of circulating miRNAs modulated by age in the long-lived Ames mouse. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
    Aging cell 07/2015; DOI:10.1111/acel.12373 · 6.34 Impact Factor
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    • "tRNAs are known to be versatile by playing various roles in gene regulation besides their main function in the translational machinery (Pederson, 2010; Sobala and Hutvagner, 2011). In this section, we will discuss Argonaute-dependent tRNA-fragments (tRFs) that are processed by Dicer-independent mechanisms or generated from precursors with no duplex structures. "
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    ABSTRACT: A general feature of Argonaute-dependent small RNAs is their base-paired precursor structures, and precursor duplex structures are often required for confident annotation of miRNA genes. However, this rule has been broken by discoveries of functional small RNA species whose precursors lack a predictable double-stranded (ds-) RNA structure, arguing that duplex structures are not prerequisite for small RNA loading to Argonautes. The biological significance of single-stranded (ss-) RNA loading has been recognized particularly in systems where active small RNA amplification mechanisms are involved, because even a small amount of RNA molecules can trigger the production of abundant RNA species leading to profound biological effects. However, even in the absence of small RNA amplification mechanisms, recent studies have demonstrated that potent gene silencing can be achieved using chemically modified synthetic ssRNAs that are resistant to RNases in mice. Therefore, such ssRNA-mediated gene regulation may have broader roles than previously recognized, and the findings have opened the door for further research to optimize the design of ss-siRNAs toward future pharmaceutical and biomedical applications of gene silencing technologies. In this review, we will summarize studies about endogenous ssRNA species that are bound by Argonaute proteins and how ssRNA precursors are recognized by various small RNA pathways.
    Frontiers in Genetics 06/2014; 5:172. DOI:10.3389/fgene.2014.00172
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    • "Interestingly, as yet another " unconventional " small RNA with regulatory functions [61] we also found piRNAs and endo-siRNAs generated from rRNA cleavage. This rRNAderived group was particularly abundant in spermatozoa. "
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    ABSTRACT: A set of small RNAs known as rasRNAs (repeat-associated small RNAs) have been related to the down-regulation of Transposable Elements (TEs) to safeguard genome integrity. Two key members of the rasRNAs group are piRNAs and endo-siRNAs. We have performed a comparative analysis of piRNAs and endo-siRNAs present in mouse oocytes, spermatozoa and zygotes, identified by deep sequencing and bioinformatic analysis. The detection of piRNAs and endo-siRNAs in spermatozoa and revealed also in zygotes, hints to their potential delivery to oocytes during fertilization. However, a comparative assessment of the three cell types indicates that both piRNAs and endo-siRNAs are mainly maternally inherited. Finally, we have assessed the role of the different rasRNA molecules in connection with amplification processes by way of the "ping-pong cycle". Our results suggest that the ping-pong cycle can act on other rasRNAs, such as tRNA- and rRNA-derived fragments, thus not only being restricted to TEs during gametogenesis.
    Biochimica et Biophysica Acta 04/2014; 1839(6). DOI:10.1016/j.bbagrm.2014.04.006 · 4.66 Impact Factor
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