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Surveillance and cleavage of eukaryotic tRNAs.

Megel C, Morelle G, Lalande S, Duchêne AM, Small I, Maréchal-Drouard L - Int J Mol Sci (2015)

Bottom Line: These cleavage products of tRNAs now potentially emerge as a new class of small non-coding RNAs (sncRNAs) and are suspected to have important regulatory functions.The tRFs are evolutionarily widespread and created by cleavage at different positions by various endonucleases.Here, we review our present knowledge on the biogenesis and function of tRFs in various organisms.

View Article: PubMed Central - PubMed

Affiliation: Institut de Biologie Moléculaire des Plantes, CNRS, Associated with University of Strasbourg, 12 rue du Général Zimmer, F-67084 Strasbourg Cedex, France. cyrille.megel@ibmp-cnrs.unistra.fr.

ABSTRACT
Beyond their central role in protein synthesis, transfer RNAs (tRNAs) have many other crucial functions. This includes various roles in the regulation of gene expression, stress responses, metabolic processes and priming reverse transcription. In the RNA world, tRNAs are, with ribosomal RNAs, among the most stable molecules. Nevertheless, they are not eternal. As key elements of cell function, tRNAs need to be continuously quality-controlled. Two tRNA surveillance pathways have been identified. They act on hypo-modified or mis-processed pre-tRNAs and on mature tRNAs lacking modifications. A short overview of these two pathways will be presented here. Furthermore, while the exoribonucleases acting in these pathways ultimately lead to complete tRNA degradation, numerous tRNA-derived fragments (tRFs) are present within a cell. These cleavage products of tRNAs now potentially emerge as a new class of small non-coding RNAs (sncRNAs) and are suspected to have important regulatory functions. The tRFs are evolutionarily widespread and created by cleavage at different positions by various endonucleases. Here, we review our present knowledge on the biogenesis and function of tRFs in various organisms.

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Overview of the two tRNA degradation pathways of S. cerevisae. This figure is adapted from [10]. (A) The tRNA nuclear surveillance pathway was primarily shown to act on pre-tRNAs lacking modifications (e.g., pre-tRNAiMet). Hypo-modified pre-tRNA is first polyadenylated by the TRAMP complex and then degraded by the exosome; (B) Degradation of mature tRNAs through the rapid tRNA decay (RTD) pathway. RTD was shown to act on hypo-modified tRNAs (marked with red crosses) (e.g., tRNAVal(AAC)). The major components are depicted. The implication of the tRNA-nucleotidyl transferase (CCAse) enzyme in the RTD pathway is also presented [33]. A, CCA triplet or a short poly(A) tail (AAAA) depicted in red can be added by the CCAse enzyme.
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ijms-16-01873-f001: Overview of the two tRNA degradation pathways of S. cerevisae. This figure is adapted from [10]. (A) The tRNA nuclear surveillance pathway was primarily shown to act on pre-tRNAs lacking modifications (e.g., pre-tRNAiMet). Hypo-modified pre-tRNA is first polyadenylated by the TRAMP complex and then degraded by the exosome; (B) Degradation of mature tRNAs through the rapid tRNA decay (RTD) pathway. RTD was shown to act on hypo-modified tRNAs (marked with red crosses) (e.g., tRNAVal(AAC)). The major components are depicted. The implication of the tRNA-nucleotidyl transferase (CCAse) enzyme in the RTD pathway is also presented [33]. A, CCA triplet or a short poly(A) tail (AAAA) depicted in red can be added by the CCAse enzyme.

Mentions: The nuclear surveillance pathway (Figure 1A) was discovered in temperature-sensitive yeast (Saccharomyces cerevisiae) strains lacking the tRNA methyl transferases (Trm) Trm6 or Trm61 (also named Gcd10 or Gcd14 for General control non-derepressible proteins 10 and 14) the two essential subunits of the methyltransferase responsible for tRNA m1A modification. In these strains, the precursor of initiator tRNAMet (pre-tRNAiMet) lacks m1A58 and is subject to rapid turnover [14,15]. In vivo genetic analyses provided evidence that as a first step towards its degradation, the pre-tRNAiMet is polyadenylated at its 3' end by the TRAMP complex. This complex was first shown to be required for polyadenylation and degradation of rRNA and snoRNA (small nucleolar RNA) precursors as part of a post-transcriptional quality control mechanism [16]. It is constituted by Trf4, a poly(A) polymerase, Mtr4, a RNA helicase, and Air2, a zinc knuckle protein interacting with Rrp6 (Ribosomal RNA Processing subunit 6), the 3' exoribonuclease of the nuclear exosome. Following polyadenylation by Trf4, pre-tRNAiMet is degraded from the 3' end by Rrp6 [10,17,18,19,20,21]. Both the TRAMP and exosome complexes are localized in the nucleus. As described above in yeast, the pre-tRNA nuclear surveillance pathway is implicated in the degradation of defective hypomodified pre-tRNAiMet. However, how a tRNA is recognized or not as a substrate to be adenylated and degraded remains largely unknown. The lack of m1A58 is per se not sufficient to explain why the pre-tRNAiMet is rapidly degraded as other tRNAs lacking the same modification are not degraded [18]. The most reasonable hypothesis is that the nuclear surveillance pathway recognizes aberrant mis-folded tRNA tertiary structure. In vitro data suggest that other tRNAs can be TRAMP substrates, but this remains to be demonstrated in vivo [16,22].


Surveillance and cleavage of eukaryotic tRNAs.

Megel C, Morelle G, Lalande S, Duchêne AM, Small I, Maréchal-Drouard L - Int J Mol Sci (2015)

Overview of the two tRNA degradation pathways of S. cerevisae. This figure is adapted from [10]. (A) The tRNA nuclear surveillance pathway was primarily shown to act on pre-tRNAs lacking modifications (e.g., pre-tRNAiMet). Hypo-modified pre-tRNA is first polyadenylated by the TRAMP complex and then degraded by the exosome; (B) Degradation of mature tRNAs through the rapid tRNA decay (RTD) pathway. RTD was shown to act on hypo-modified tRNAs (marked with red crosses) (e.g., tRNAVal(AAC)). The major components are depicted. The implication of the tRNA-nucleotidyl transferase (CCAse) enzyme in the RTD pathway is also presented [33]. A, CCA triplet or a short poly(A) tail (AAAA) depicted in red can be added by the CCAse enzyme.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4307339&req=5

ijms-16-01873-f001: Overview of the two tRNA degradation pathways of S. cerevisae. This figure is adapted from [10]. (A) The tRNA nuclear surveillance pathway was primarily shown to act on pre-tRNAs lacking modifications (e.g., pre-tRNAiMet). Hypo-modified pre-tRNA is first polyadenylated by the TRAMP complex and then degraded by the exosome; (B) Degradation of mature tRNAs through the rapid tRNA decay (RTD) pathway. RTD was shown to act on hypo-modified tRNAs (marked with red crosses) (e.g., tRNAVal(AAC)). The major components are depicted. The implication of the tRNA-nucleotidyl transferase (CCAse) enzyme in the RTD pathway is also presented [33]. A, CCA triplet or a short poly(A) tail (AAAA) depicted in red can be added by the CCAse enzyme.
Mentions: The nuclear surveillance pathway (Figure 1A) was discovered in temperature-sensitive yeast (Saccharomyces cerevisiae) strains lacking the tRNA methyl transferases (Trm) Trm6 or Trm61 (also named Gcd10 or Gcd14 for General control non-derepressible proteins 10 and 14) the two essential subunits of the methyltransferase responsible for tRNA m1A modification. In these strains, the precursor of initiator tRNAMet (pre-tRNAiMet) lacks m1A58 and is subject to rapid turnover [14,15]. In vivo genetic analyses provided evidence that as a first step towards its degradation, the pre-tRNAiMet is polyadenylated at its 3' end by the TRAMP complex. This complex was first shown to be required for polyadenylation and degradation of rRNA and snoRNA (small nucleolar RNA) precursors as part of a post-transcriptional quality control mechanism [16]. It is constituted by Trf4, a poly(A) polymerase, Mtr4, a RNA helicase, and Air2, a zinc knuckle protein interacting with Rrp6 (Ribosomal RNA Processing subunit 6), the 3' exoribonuclease of the nuclear exosome. Following polyadenylation by Trf4, pre-tRNAiMet is degraded from the 3' end by Rrp6 [10,17,18,19,20,21]. Both the TRAMP and exosome complexes are localized in the nucleus. As described above in yeast, the pre-tRNA nuclear surveillance pathway is implicated in the degradation of defective hypomodified pre-tRNAiMet. However, how a tRNA is recognized or not as a substrate to be adenylated and degraded remains largely unknown. The lack of m1A58 is per se not sufficient to explain why the pre-tRNAiMet is rapidly degraded as other tRNAs lacking the same modification are not degraded [18]. The most reasonable hypothesis is that the nuclear surveillance pathway recognizes aberrant mis-folded tRNA tertiary structure. In vitro data suggest that other tRNAs can be TRAMP substrates, but this remains to be demonstrated in vivo [16,22].

Bottom Line: These cleavage products of tRNAs now potentially emerge as a new class of small non-coding RNAs (sncRNAs) and are suspected to have important regulatory functions.The tRFs are evolutionarily widespread and created by cleavage at different positions by various endonucleases.Here, we review our present knowledge on the biogenesis and function of tRFs in various organisms.

View Article: PubMed Central - PubMed

Affiliation: Institut de Biologie Moléculaire des Plantes, CNRS, Associated with University of Strasbourg, 12 rue du Général Zimmer, F-67084 Strasbourg Cedex, France. cyrille.megel@ibmp-cnrs.unistra.fr.

ABSTRACT
Beyond their central role in protein synthesis, transfer RNAs (tRNAs) have many other crucial functions. This includes various roles in the regulation of gene expression, stress responses, metabolic processes and priming reverse transcription. In the RNA world, tRNAs are, with ribosomal RNAs, among the most stable molecules. Nevertheless, they are not eternal. As key elements of cell function, tRNAs need to be continuously quality-controlled. Two tRNA surveillance pathways have been identified. They act on hypo-modified or mis-processed pre-tRNAs and on mature tRNAs lacking modifications. A short overview of these two pathways will be presented here. Furthermore, while the exoribonucleases acting in these pathways ultimately lead to complete tRNA degradation, numerous tRNA-derived fragments (tRFs) are present within a cell. These cleavage products of tRNAs now potentially emerge as a new class of small non-coding RNAs (sncRNAs) and are suspected to have important regulatory functions. The tRFs are evolutionarily widespread and created by cleavage at different positions by various endonucleases. Here, we review our present knowledge on the biogenesis and function of tRFs in various organisms.

Show MeSH
Related in: MedlinePlus