Transfer RNA Post-Transcriptional Processing, Turnover, and Subcellular Dynamics in the Yeast<i>Saccharomyces cerevisiae</i>

Hopper, Anita K.

doi:10.1534/genetics.112.147470

Cited by 175 publications

(201 citation statements)

References 243 publications

(320 reference statements)

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“…It is possible, therefore, that the TgPUS1-dependent Ψ's affecting differentiation are found in tRNA(s). If changes in pseudouridylation change expression or processing of tRNAs, tRNA cleavage products that act as regulatory molecules could indirectly affect the cellular pool of mRNAs, producing the changes we observed in TgPUS1-deficient parasites (Phizicky and Hopper 2010;Galizi et al 2013;Hopper 2013).…”

Section: Discussionmentioning

confidence: 89%

mRNA pseudouridylation affects RNA metabolism in the parasite Toxoplasma gondii

Nakamoto

Lovejoy

Cygan

et al. 2017

RNA

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RNA contains over 100 modified nucleotides that are created post-transcriptionally, among which pseudouridine (Ψ) is one of the most abundant. Although it was one of the first modifications discovered, the biological role of this modification is still not fully understood. Recently, we reported that a pseudouridine synthase (TgPUS1) is necessary for differentiation of the singlecelled eukaryotic parasite Toxoplasma gondii from active to chronic infection. To better understand the biological role of pseudouridylation, we report here gel-based and deep-sequencing methods to identify TgPUS1-dependent Ψ's in Toxoplasma RNA, and the use of TgPUS1 mutants to examine the effect of this modification on mRNAs. In addition to identifying conserved sites of pseudouridylation in Toxoplasma rRNA, tRNA, and snRNA, we also report extensive pseudouridylation of Toxoplasma mRNAs, with the Ψ's being relatively depleted in the 3 ′ ′ ′ ′ ′ -UTR but enriched at position 1 of codons. We show that many Ψ's in tRNA and mRNA are dependent on the action of TgPUS1 and that TgPUS1-dependent mRNA Ψ's are enriched in developmentally regulated transcripts. RNA-seq data obtained from wild-type and TgPUS1-mutant parasites shows that genes containing a TgPUS1-dependent Ψ are relatively more abundant in mutant parasites, while pulse/chase labeling of RNA with 4-thiouracil shows that mRNAs containing TgPUS1-dependent Ψ have a modest but statistically significant increase in half-life in the mutant parasites. These data are some of the first evidence suggesting that mRNA Ψ's play an important biological role.

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Section: Discussionmentioning

confidence: 89%

mRNA pseudouridylation affects RNA metabolism in the parasite Toxoplasma gondii

Nakamoto

Lovejoy

Cygan

et al. 2017

RNA

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“…2) (Drygin and others 2010). Similarly, Pol-III generates a subset of additional RNAs comprising transfer RNA (tRNA), some small nucleolar RNA (snoRNAs), 5S rRNA, 7SK RNA, and U6 snRNA (Hopper 2013;Kirchner and Ignatova 2015). Like Pol-I transcribed rRNAs, tRNAs bear a 5¢ P after cleavage of a 5¢ oligonucleotide.…”

Section: Generation and Properties Of Cellular Rnamentioning

confidence: 99%

Discrimination of Self and Non-Self Ribonucleic Acids

Gebhardt

Laudenbach

Pichlmair

2017

Journal of Interferon & Cytokine Research

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Most virus infections are controlled through the innate and adaptive immune system. A surprisingly limited number of so-called pattern recognition receptors (PRRs) have the ability to sense a large variety of virus infections. The reason for the broad activity of PRRs lies in the ability to recognize viral nucleic acids. These nucleic acids lack signatures that are present in cytoplasmic cellular nucleic acids and thereby marking them as pathogen-derived. Accumulating evidence suggests that these signatures, which are predominantly sensed by a class of PRRs called retinoic acid-inducible gene I (RIG-I)-like receptors and other proteins, are not unique to viruses but rather resemble immature forms of cellular ribonucleic acids generated by cellular polymerases. RIG-I-like receptors, and other cellular antiviral proteins, may therefore have mainly evolved to sense nonprocessed nucleic acids typically generated by primitive organisms and pathogens. This capability has not only implications on induction of antiviral immunity but also on the function of cellular proteins to handle selfderived RNA with stimulatory potential.

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“…Finally, an isoacceptor-isodecoder species may, in turn, exhibit diverse states of modification. Therefore, a particular tRNA species could be partitioned in a number of variants or subspecies (Hopper 2013).…”

Section: The State Of the Trna Population In The Cellmentioning

confidence: 99%

Protein folding and tRNA biology

2017

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Polypeptides can fold into tertiary structures while they are synthesized by the ribosome. In addition to the amino acid sequence, protein folding is determined by several factors within the cell. Among others, the folding pathway of a nascent polypeptide can be affected by transient interactions with other proteins, ligands, or the ribosome, as well as by the translocation through membrane pores. Particularly, the translation machinery and the population of tRNA under different physiological or adaptive responses can dramatically affect protein folding. This review summarizes the scientific evidence describing the role of translation kinetics and tRNA populations on protein folding and addresses current efforts to better understand tRNA biology. It is organized into three main parts, which are focused on: (i) protein folding in the cellular context; (ii) tRNA biology and the complexity of the tRNA population; and (iii) available methods and technical challenges in the characterization of tRNA pools. In this manner, this work illustrates the ways by which functional properties of proteins may be modulated by cellular tRNA populations.

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Transfer RNA Post-Transcriptional Processing, Turnover, and Subcellular Dynamics in the YeastSaccharomyces cerevisiae

Cited by 175 publications

References 243 publications

mRNA pseudouridylation affects RNA metabolism in the parasite Toxoplasma gondii

mRNA pseudouridylation affects RNA metabolism in the parasite Toxoplasma gondii

Discrimination of Self and Non-Self Ribonucleic Acids

Protein folding and tRNA biology

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