The yeast rapid tRNA decay pathway primarily monitors the structural integrity of the acceptor and T-stems of mature tRNA

Whipple, Joseph M.; Lane, Elizabeth A.; Chernyakov, Irina; D’Silva, Sonia; Phizicky, Eric M.

doi:10.1101/gad.2050711

Cited by 132 publications

(181 citation statements)

References 55 publications

(72 reference statements)

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“…Rapid tRNA Decay. Additional levels of tRNA quality control involve the degradation of improper tRNAs by both the nuclear surveillance pathway (37,38) and the RTD pathway (39)(40)(41). To learn whether the aberrant tRNAs that we identified are substrates for cytoplasmic RTD by the 5′-3′ exonuclease Xrn1, we used RT-PCR studies in xrn1Δ cells.…”

Section: Resultsmentioning

confidence: 99%

“…The cytoplasmic RTD pathway monitors the tRNA tertiary structure, degrading tRNAs that possess destabilized acceptor and T stems, often because they lack certain modification(s) (39)(40)(41). Lack of some modifications may not decrease tRNA stability, and therefore some hypomodified tRNAs that have mistakenly been exported to the cytoplasm may be unrecognized by the cytoplasmic RTD pathway.…”

Section: Discussionmentioning

confidence: 99%

“…A nuclear surveillance pathway monitors pre-tRNAs and polyadenylates and degrades initiator tRNA (37,38) as well as tRNAs with unprocessed 3′ ends (7,8). The rapid tRNA decay (RTD) pathway monitors mature tRNAs in both the nucleus and the cytoplasm, degrading those that are destabilized in structure (39)(40)(41).…”

Section: Significancementioning

confidence: 99%

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Retrograde transfer RNA nuclear import provides a new level of tRNA quality control in Saccharomyces cerevisiae

Kramer

Hopper

2013

Proc. Natl. Acad. Sci. U.S.A.

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In eukaryotes, transfer RNAs (tRNAs) are transcribed in the nucleus yet function in the cytoplasm; thus, tRNA movement within the cell was believed to be unidirectional-from the nucleus to the cytoplasm. It is now known that mature tRNAs also move in a retrograde direction from the cytoplasm to the nucleus via retrograde tRNA nuclear import, a process that is conserved from yeast to vertebrates. The biological significance of this tRNA nuclear import is not entirely clear. We hypothesized that retrograde tRNA nuclear import might function in proofreading tRNAs to ensure that only proper tRNAs reside in the cytoplasm and interact with the translational machinery. Here we identify two major types of aberrant tRNAs in yeast: a 5′, 3′ end-extended, spliced tRNA and hypomodified tRNAs. We show that both types of aberrant tRNAs accumulate in mutant cells that are defective in tRNA nuclear traffic, suggesting that they are normally imported into the nucleus and are repaired or degraded. The retrograde pathway functions in parallel with the cytoplasmic rapid tRNA decay pathway previously demonstrated to monitor tRNA quality, and cells are not viable if they lack both pathways. Our data support the hypothesis that the retrograde process provides a newly discovered level of tRNA quality control as a pathway that monitors both end processing of pre-tRNAs and the modification state of mature tRNAs.tRNA retrograde pathway | tRNA processing errors | quality control pathways | Mtr10 | Los1 T ransfer RNAs (tRNAs) are well known for their role as adaptor molecules during the translation of mRNAs into proteins, delivering amino acids to the ribosome for incorporation into a polypeptide chain. In eukaryotes, tRNAs are transcribed in the nucleus as primary transcripts that undergo extensive processing, chemical modification, and subcellular trafficking to produce the mature tRNAs that function in cytoplasmic translation. In the yeast Saccharomyces cerevisiae, tRNA transcription in the nucleolus (1), with one exception (2), is followed by removal of the 5′ leader sequence by RNase P (3). The 3′ trailer is subsequently removed endonucleolytically, presumably by tRNase Z (4-6), and/or exonucleolytically by Rex1 (7,8). Following removal of the 3′ trailer, the nucleotides C 74 C 75 A 76 , necessary for tRNA aminoacylation, are added to the 3′ terminus. Twenty percent of yeast tRNAs are transcribed with an intron (9). Splicing of tRNA introns occurs in the cytoplasm in yeast, on the outer surface of mitochondria where the tRNA splicing endonuclease complex resides (10-12). Thus, end-processed intron-containing tRNAs are exported from the nucleus to the cytoplasm before removal of the intron. This primary export of intron-containing pre-tRNA is mediated by the β-importin family member Los1 (13-15). Because LOS1 is unessential and because it is essential to have tRNAs delivered to the cytoplasm, there is at least one additional unidentified nuclear exporter for end-processed intron-containing pre-tRNA (16).tRNAs are subject to numerous pos...

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Retrograde transfer RNA nuclear import provides a new level of tRNA quality control in Saccharomyces cerevisiae

Kramer

Hopper

2013

Proc. Natl. Acad. Sci. U.S.A.

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“…However, the RTD machinery does not degrade some unmodified tRNAs that normally bear the relevant modifications. To address this problem, Whipple et al (2011) compared two tRNA Ser species, both of which are modified by Trm44 and Tan1, but one, tRNA Ser IGA , is not a RTD substrate, whereas the other, tRNA Ser CGA , is a RTD target. In vivo and in vitro data showed that tRNA Ser CGA gained immunity to RTD when nucleotides of tRNA Ser CGA were replaced with tRNA Ser IGA nucleotides that enhanced the stability of the acceptor and T-stems.…”

Section: To 39 Exonucleolyic Degradation By the Rtd Pathwaymentioning

confidence: 99%

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

2013

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Transfer RNAs (tRNAs) are essential for protein synthesis. In eukaryotes, tRNA biosynthesis employs a specialized RNA polymerase that generates initial transcripts that must be subsequently altered via a multitude of post-transcriptional steps before the tRNAs beome mature molecules that function in protein synthesis. Genetic, genomic, biochemical, and cell biological approaches possible in the powerful Saccharomyces cerevisiae system have led to exciting advances in our understandings of tRNA post-transcriptional processing as well as to novel insights into tRNA turnover and tRNA subcellular dynamics. tRNA processing steps include removal of transcribed leader and trailer sequences, addition of CCA to the 39 mature sequence and, for tRNA His , addition of a 59 G. About 20% of yeast tRNAs are encoded by intron-containing genes. The three-step splicing process to remove the introns surprisingly occurs in the cytoplasm in yeast and each of the splicing enzymes appears to moonlight in functions in addition to tRNA splicing. There are 25 different nucleoside modifications that are added post-transcriptionally, creating tRNAs in which 15% of the residues are nucleosides other than A, G, U, or C. These modified nucleosides serve numerous important functions including tRNA discrimination, translation fidelity, and tRNA quality control. Mature tRNAs are very stable, but nevertheless yeast cells possess multiple pathways to degrade inappropriately processed or folded tRNAs. Mature tRNAs are also dynamic in cells, moving from the cytoplasm to the nucleus and back again to the cytoplasm; the mechanism and function of this retrograde process is poorly understood. Here, the state of knowledge for tRNA post-transcriptional processing, turnover, and subcellular dynamics is addressed, highlighting the questions that remain. TABLE OF CONTENTS Abstract 43Introduction 44

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“…The nuclear surveillance pathway provides one mechanism; pre-tRNA Met i lacking m 1 A 58 and pre-tRNAs with aberrant 39 ends are polyadenylated by the TRAMP complex and further degraded by the nuclear exosome (Kabada et al 2004;Copela et al 2008;Ozanick et al 2009). The other pathway, the rapid tRNA decay (RTD) pathway, destroys mature tRNAs that lack certain combinations of modifications or tRNAs that bear unstable T or acceptor stems (Chernyakov et al 2008;Whipple et al 2011).…”

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confidence: 99%

Healing for destruction: tRNA intron degradation in yeast is a two-step cytoplasmic process catalyzed by tRNA ligase Rlg1 and 5′-to-3′ exonuclease Xrn1

Hopper

2014

Genes Dev.

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In eukaryotes and archaea, tRNA splicing generates free intron molecules. Although~600,000 introns are produced per generation in yeast, they are barely detectable in cells, indicating efficient turnover of introns. Through a genome-wide search for genes involved in tRNA biology in yeast, we uncovered the mechanism for intron turnover. This process requires healing of the 59 termini of linear introns by the tRNA ligase Rlg1 and destruction by the cytoplasmic tRNA quality control 59-to-39 exonuclease Xrn1, which has specificity for RNAs with 59 monophosphate.

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The yeast rapid tRNA decay pathway primarily monitors the structural integrity of the acceptor and T-stems of mature tRNA

Cited by 132 publications

References 55 publications

Retrograde transfer RNA nuclear import provides a new level of tRNA quality control in Saccharomyces cerevisiae

Retrograde transfer RNA nuclear import provides a new level of tRNA quality control in Saccharomyces cerevisiae

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

Healing for destruction: tRNA intron degradation in yeast is a two-step cytoplasmic process catalyzed by tRNA ligase Rlg1 and 5′-to-3′ exonuclease Xrn1

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