Quality Control Pathways for Nucleus-Encoded Eukaryotic tRNA Biosynthesis and Subcellular Trafficking

Hopper, Anita K.; Huang, Hsiao-Yun

doi:10.1128/mcb.00131-15

Cited by 43 publications

(36 citation statements)

References 75 publications

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“…5C). We can exclude a differential role for introns in this specificity because tRNA Ser GCU, tRNA Ser CGA, and tRNA Ser UGA contain introns while tRNA Ser AGA does not; from this can also be inferred that m 3 C32 modification must occur in the cytoplasm or require retrograde transport of spliced tRNA to the nucleus (Hopper and Huang 2015). Specificity provided by tRNA Ser GCU allows another conclusion.…”

Section: A New Acl Modification Circuitmentioning

confidence: 84%

Evolving specificity of tRNA 3-methyl-cytidine-32 (m³C32) modification: a subset of tRNAs^Ser requires N⁶-isopentenylation of A37

Arimbasseri

Iben

Wei

et al. 2016

RNA

113

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Post-transcriptional modifications of anticodon loop (ACL) nucleotides impact tRNA structure, affinity for the ribosome, and decoding activity, and these activities can be fine-tuned by interactions between nucleobases on either side of the anticodon. A recently discovered ACL modification circuit involving positions 32, 34, and 37 is disrupted by a human disease-associated mutation to the gene encoding a tRNA modification enzyme. We used tRNA-HydroSeq (-HySeq) to examine 3 methyl-cytidine-32 (m 3 C32), which is found in yeast only in the ACLs of tRNAs Ser and tRNAs Thr . In contrast to that reported for Saccharomyces cerevisiae in which all m 3 C32 depends on a single gene, TRM140, the m 3 C32 of tRNAs Ser and tRNAs Thr of the fission yeast S. pombe, are each dependent on one of two related genes, trm140 + and trm141 + , homologs of which are found in higher eukaryotes. Interestingly, mammals and other vertebrates contain a third homolog and also contain m 3 C at new sites, positions 32 on tRNAs Arg and C47:3 in the variable arm of tRNAs Ser . More significantly, by examining S. pombe mutants deficient for other modifications, we found that m 3 C32 on the three tRNAs Ser that contain anticodon base A36, requires N 6 -isopentenyl modification of A37 (i 6 A37). This new C32-A37 ACL circuitry indicates that i 6 A37 is a pre-or corequisite for m 3 C32 on these tRNAs. Examination of the tRNA database suggests that such circuitry may be more expansive than observed here. The results emphasize two contemporary themes, that tRNA modifications are interconnected, and that some specific modifications on tRNAs of the same anticodon identity are species-specific.

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Section: A New Acl Modification Circuitmentioning

confidence: 84%

Evolving specificity of tRNA 3-methyl-cytidine-32 (m³C32) modification: a subset of tRNAs^Ser requires N⁶-isopentenylation of A37

Arimbasseri

Iben

Wei

et al. 2016

RNA

113

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“…While quality control pathways are well characterized for coding mRNAs (Garneau et al, 2007), tRNAs (Hopper and Huang, 2015; Kadaba et al, 2006; Vanacova et al, 2005) and rRNAs (Dez et al, 2006; LaRiviere et al, 2006), far less is known about the existence of such mechanisms for other ncRNAs. Quality control mechanisms have been proposed for truncated (Ishikawa et al, 2014) or mutant forms of U1 snRNA (Shukla and Parker, 2014) and 7SL in yeast (Leung et al, 2014) to eliminate aberrant transcripts.…”

Section: Discussionmentioning

confidence: 99%

Dis3l2-Mediated Decay Is a Quality Control Pathway for Noncoding RNAs

et al. 2016

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SUMMARY Mutations in the 3′-5′ exonuclease DIS3L2 are associated with Perlman syndrome and hypersusceptibility to Wilms’ tumorigenesis. Previously, we found that Dis3l2 specifically recognizes and degrades uridylated pre-let-7 microRNA. However, the widespread relevance of Dis3l2-mediated decay of uridylated substrates remains unknown. Here we applied an unbiased RNA immunoprecipitation strategy to identify Dis3l2 targets in mouse embryonic stem cells. The disease-associated long noncoding RNA (lncRNA) Rmrp, 7SL, as well as several other Pol III-transcribed noncoding RNAs (ncRNAs) were among the most highly enriched Dis3l2-bound RNAs. 3′-uridylated Rmrp, 7SL, and snRNA species were highly stabilized in the cytoplasm of Dis3l2-depleted cells. Deep sequencing analysis of Rmrp 3′ ends revealed extensive oligouridylation mainly on transcripts with imprecise ends. We implicate the TUTases Zcchc6/11 in the uridylation of these ncRNAs, and biochemical reconstitution assays demonstrate the sufficiency of TUTase-Dis3l2 for Rmrp decay. This establishes Dis3l2-Mediated Decay (DMD) as a quality control pathway that eliminates aberrant ncRNAs.

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“…S3). As tRNAs are spliced in the cytoplasm (Hopper and Huang 2015), it is also unlikely that Nab2 is required for nuclear tRNA export. Taken together, Nab2 might have two functions in RNAPIII transcription: One in initiation, as shown here, and a second one in elongation based on its interaction with precursors of RNPIII transcripts.…”

Section: Discussionmentioning

confidence: 99%

The poly(A)-binding protein Nab2 functions in RNA polymerase III transcription

2015

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RNA polymerase III (RNAPIII) synthesizes most small RNAs, the most prominent being tRNAs. Although the basic mechanism of RNAPIII transcription is well understood, recent evidence suggests that additional proteins play a role in RNAPIII transcription. Here, we discovered by a genome-wide approach that Nab2, a poly(A)-binding protein important for correct poly(A) tail length and nuclear mRNA export, is present at all RNAPIII transcribed genes. The occupancy of Nab2 at RNAPIII transcribed genes is dependent on transcription. Using a novel temperature-sensitive allele of NAB2, nab2-34, we show that Nab2 is required for the occupancy of RNAPIII and TFIIIB at target genes. Furthermore, Nab2 interacts with RNAPIII, TFIIIB, and RNAPIII transcripts. Importantly, impairment of Nab2 function causes an RNAPIII transcription defect in vivo and in vitro. Taken together, we establish Nab2, an important mRNA biogenesis factor, as a novel player required for RNAPIII transcription by stabilizing TFIIIB and RNAPIII at promoters.[Keywords: RNA polymerase III; Nab2; tRNA; ncRNA; gene expression; TFIIIB] Supplemental material is available for this article. RNA polymerase III (RNAPIII) is responsible for the production of most noncoding RNAs (ncRNAs) such as tRNAs, the 5S rRNA (encoded by RDN5), the RNA of the signal recognition particle (SCR1), the spliceosomal U6 snRNA (SNR6), and the RNA component of RNase P (RPR1). Transcription by RNAPIII is initiated at three classes of promoters, which are highly diverse, have a relatively small number of cis-acting elements, and require comparably few transcription factors (TFs) (White 2011;Orioli et al. 2012;Acker et al. 2013 and references therein). Type 1 promoters are exclusively present at 5S rRNA-encoding genes (RN5S in mammals, and RDN5 in yeast). Type 1 promoters have three internal elements: the A box, which is recognized by TFIIIC, and the intermediate element (IE) and the C box, which are recognized by TFIIIA. The most common RNAPIII promoters are of type 2 and drive transcription of tRNA genes as well as, e.g., the SCR1 and RPR1 genes. Type 2 promoters consist of A-and B-box elements, which together recruit TFIIIC. TFIIIC recruits TFIIIB to the transcription start site at type 1 and type 2 promoters. Type 3 promoters are relatively rare, and, in contrast to type 1 and 2 promoters, all of their elements lie 5 ′ of the transcription start site: the distal sequence element (DSE), the proximal sequence element (PSE), and the TATA box. The DSE recruits the TFs Oct1 and STAF, whereas the PSE recruits SNAP c , which in turn binds TFIIIB and recruits it together with the TATA box to the promoter (Schramm and Hernandez 2002 and references therein). Type 3 promoters are only present in vertebrates; e.g., at the U6 snRNA gene. The promoter of the Saccharomyces cerevisiae U6 snRNA gene SNR6 is of type 2 and contains an upstream TATA box in addition to the canonical A and B boxes (Brow and Guthrie 1990;Eschenlauer et al. 1993). At all three types of promoters, TFIIIB recruits RNAPIII. TFIIIB i...

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Quality Control Pathways for Nucleus-Encoded Eukaryotic tRNA Biosynthesis and Subcellular Trafficking

Cited by 43 publications

References 75 publications

Evolving specificity of tRNA 3-methyl-cytidine-32 (m³C32) modification: a subset of tRNAs^Ser requires N⁶-isopentenylation of A37

Evolving specificity of tRNA 3-methyl-cytidine-32 (m³C32) modification: a subset of tRNAs^Ser requires N⁶-isopentenylation of A37

Dis3l2-Mediated Decay Is a Quality Control Pathway for Noncoding RNAs

The poly(A)-binding protein Nab2 functions in RNA polymerase III transcription

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Quality Control Pathways for Nucleus-Encoded Eukaryotic tRNA Biosynthesis and Subcellular Trafficking

Cited by 43 publications

References 75 publications

Evolving specificity of tRNA 3-methyl-cytidine-32 (m3C32) modification: a subset of tRNAsSer requires N6-isopentenylation of A37

Evolving specificity of tRNA 3-methyl-cytidine-32 (m3C32) modification: a subset of tRNAsSer requires N6-isopentenylation of A37

Dis3l2-Mediated Decay Is a Quality Control Pathway for Noncoding RNAs

The poly(A)-binding protein Nab2 functions in RNA polymerase III transcription

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Evolving specificity of tRNA 3-methyl-cytidine-32 (m³C32) modification: a subset of tRNAs^Ser requires N⁶-isopentenylation of A37

Evolving specificity of tRNA 3-methyl-cytidine-32 (m³C32) modification: a subset of tRNAs^Ser requires N⁶-isopentenylation of A37