tRNA biology charges to the front

Department of Biochemistry and Biophysics, Center for RNA Biology, University of Rochester School of Medicine, Rochester, New York 14642, USA.
Genes & development (Impact Factor: 10.8). 09/2010; 24(17):1832-60. DOI: 10.1101/gad.1956510
Source: PubMed


tRNA biology has come of age, revealing an unprecedented level of understanding and many unexpected discoveries along the way. This review highlights new findings on the diverse pathways of tRNA maturation, and on the formation and function of a number of modifications. Topics of special focus include the regulation of tRNA biosynthesis, quality control tRNA turnover mechanisms, widespread tRNA cleavage pathways activated in response to stress and other growth conditions, emerging evidence of signaling pathways involving tRNA and cleavage fragments, and the sophisticated intracellular tRNA trafficking that occurs during and after biosynthesis.

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    • "With the realization that less than 3 % of the transcribed human genome is translated into protein, there has been a surge of interest in the role of the non-coding RNA transcriptome and its contribution to pathogenesis1234. Among the types of human non-coding RNAs, micro- RNAs (miRNAs) and long non-coding RNAs (lncRNAs) have been extensively studied in cancer56789101112131415161718192021(Fig. 1). "
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    ABSTRACT: PIWI-interacting RNAs (piRNAs) are emerging players in cancer genomics. Originally described in the germline, there are over 20,000 piRNA genes in the human genome. In contrast to microRNAs, piRNAs interact with PIWI proteins, another member of the Argonaute family, and function primarily in the nucleus. There, they are involved in the epigenetic silencing of transposable elements in addition to the transcriptional regulation of genes. It has recently been demonstrated that piRNAs are also expressed across a variety of human somatic tissue types in a tissue-specific manner. An increasing number of studies have shown that aberrant piRNA expression is a signature feature across multiple tumour types; however, their specific tumorigenic functions remain unclear. In this article, we discuss the emerging functional roles of piRNAs in a variety of cancers, and highlight their potential clinical utilities.
    Full-text · Article · Dec 2016 · Molecular Cancer
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    • "After end-maturation and nuclear export, splicing of intron-containing precursors occurs in the cytoplasm (Hopper 2013). Throughout all the maturation steps, modifications are added; the modified nucleotides serve numerous functions including an important role in maintaining proper tRNA structure and stability (Phizicky and Hopper 2010). Turnover of tRNA maturation intermediates is controlled by the nuclear exosome. "
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    ABSTRACT: tRNA is essential for translation and decoding of the proteome. The yeast proteome responds to stress and tRNA biosynthesis contributes in this response by repression of tRNA transcription and alterations of tRNA modification. Here we report that the stress response also involves processing of pre-tRNA 3' termini. By a combination of Northern analyses and RNA sequencing, we show that upon shift to elevated temperatures and/or to glycerol-containing medium, aberrant pre-tRNAs accumulate in yeast cells. For pre-tRNAUAU (Ile) and pre-tRNAUUU (Lys) these aberrant forms are unprocessed at the 5' ends, but they possess extended 3' termini. Sequencing analyses showed that partial 3' processing precedes 5' processing for pre-tRNAUAU (Ile). An aberrant pre-tRNA(Tyr) that accumulates also possesses extended 3' termini, but it is processed at the 5' terminus. Similar forms of these aberrant pre-tRNAs are detected in the rex1Δ strain that is defective in 3' exonucleolytic trimming of pre-tRNAs but are absent in the lhp1Δ mutant lacking 3' end protection. We further show direct correlation between the inhibition of 3' end processing rate and the stringency of growth conditions. Moreover, under stress conditions Rex1 nuclease seems to be limiting for 3' end processing, by decreased availability linked to increased protection by Lhp1. Thus, our data document complex 3' processing that is inhibited by stress in a tRNA-type and condition-specific manner. This stress-responsive tRNA 3' end maturation process presumably contributes to fine-tune the levels of functional tRNA in budding yeast in response to environmental conditions.
    Full-text · Article · Jan 2016 · RNA
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    • "[21– 23]). During their nuclear biogenesis, pre-tRNAs undergo various maturation steps including cleavage of the 5′ leader sequence by RNase P, RNase Z-dependent 3′ end processing, 3′ CCA addition and introduction of a myriad of nucleotide modifications (reviewed in Ref. [24]). Interestingly, in yeast, splicing of intron-containing tRNAs takes place on the mitochondrial outer surface [25] [26], whereas in mammalian cells, the tRNA splicing machinery is located within the nucleus [27] and intron removal takes place prior to export through the NPC. "
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    ABSTRACT: RNAs and ribonucleoprotein complexes (RNPs) play key roles in mediating and regulating gene expression. In eukaryotes, most RNAs are transcribed, processed and assembled with proteins in the nucleus and then either function in the cytoplasm or also undergo a cytoplasmic phase in their biogenesis. This compartmentalisation ensures that sequential steps in gene expression and RNP production are performed in the correct order and allows important quality control mechanisms that prevent the involvement of aberrant RNAs/RNPs in these cellular pathways. The selective exchange of RNAs/RNPs between the nucleus and cytoplasm is enabled by nuclear pore complexes (NPCs), which function as gateways between these compartments. RNA/RNP transport is facilitated by a range of nuclear transport receptors and adaptors, which are specifically recruited to their cargos and mediate interactions with nucleoporins to allow directional translocation through NPCs. While some transport factors are only responsible for the export/import of a certain class of RNA/RNP, others are multifunctional and, in the case of large RNPs, several export factors appear to work together to bring about export. Recent structural studies have revealed aspects of the mechanisms employed by transport receptors to enable specific cargo recognition, and genome-wide approaches have provided the first insights into the diverse composition of pre-mRNPs during export. Furthermore, the regulation of RNA/RNP export is emerging as an important means to modulate gene expression in stress conditions and disease.
    Full-text · Article · Oct 2015 · Journal of Molecular Biology
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