Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.13.1 (exoribonuclease)
 732 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Promoter escape can be rate-limiting for transcription by bacterial RNA polymerases and RNA polymerase II of higher eukaryotes. Formation of a productive elongation complex requires disengagement of RNA polymerase from promoter-bound eukaryotic transcription factors or bacterial sigma factors. RNA polymerase III (pol III) stably associates with the TFIIIB-DNA complex even in the absence of localized DNA unwinding associated with the open promoter complex. To explore the role that release of pol III from the TFIIIB-DNA complex plays in limiting the overall rate of transcription, we have examined the early steps of RNA synthesis. We find that, on average, only three rounds of abortive initiation precede the formation of each elongation complex and that nearly all pol III molecules escape the abortive initiation phase of transcription without significant pausing or arrest. However, when elongation is limited to 5 nucleotides, the intrinsic exoribonuclease activity of pol III cleaves 5-mer RNA at a rate considerably faster than product release or reinitiation. This cleavage also occurs in the normal process of forming a productive elongation complex. The possible role of nucleolytic retraction in disengaging pol III from TFIIIB is discussed.
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PMID:Abortive initiation by Saccharomyces cerevisiae RNA polymerase III. 1047 18

The tRNA m(1)A58 methyltransferase is composed of two subunits encoded by the essential genes TRM6 and TRM61 (formerly GCD10 and GCD14). The trm6-504 mutation results in a defective m(1)A methyltransferase (Mtase) and a temperature-sensitive growth phenotype that is attributable to the absence of m(1)A58 and consequential tRNA(i)(Met) instability. We used a genetic approach to identify the genes responsible for tRNA(i)(Met) degradation in trm6 cells. Three recessive extragenic mutations that suppress trm6-504 mutant phenotypes and restore hypomodified tRNA(i)(Met) to near normal levels were identified. The wild-type allele of one suppressor, DIS3/RRP44, encodes a 3'-5' exoribonuclease and a member of the multisubunit exosome complex. We provide evidence that a functional nuclear exosome is required for the degradation of tRNA(i)(Met) lacking m(1)A58. A second suppressor gene encodes Trf4p, a DNA polymerase (pol sigma) with poly(A) polymerase activity. Whereas deletion of TRF4 leads to stabilization of tRNA(i)(Met), overexpression of Trf4p destabilizes the hypomodified tRNA(i)(Met) in trm6 cells. The hypomodified, but not wild-type, pre-tRNA(i)(Met) accumulates as a polyadenylated species, whose abundance and length distribution both increase upon Trf4p overexpression. These data indicate that a tRNA surveillance pathway exists in yeast that requires Trf4p and the exosome for polyadenylation and degradation of hypomodified pre-tRNA(i)(Met).
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PMID:Nuclear surveillance and degradation of hypomodified initiator tRNAMet in S. cerevisiae. 1514 28

The exosome-independent exoribonuclease DIS3L2 is mutated in Perlman syndrome. Here, we used extensive global transcriptomic and targeted biochemical analyses to identify novel DIS3L2 substrates in human cells. We show that DIS3L2 regulates pol II transcripts, comprising selected canonical and histone-coding mRNAs, and a novel FTL_short RNA from the ferritin mRNA 5' UTR. Importantly, DIS3L2 contributes to surveillance of maturing snRNAs during their cytoplasmic processing. Among pol III transcripts, DIS3L2 particularly targets vault and Y RNAs and an Alu-like element BC200 RNA, but not Alu repeats, which are removed by exosome-associated DIS3. Using 3' RACE-Seq, we demonstrate that all novel DIS3L2 substrates are uridylated in vivo by TUT4/TUT7 poly(U) polymerases. Uridylation-dependent DIS3L2-mediated decay can be recapitulated in vitro, thus reinforcing the tight cooperation between DIS3L2 and TUTases. Together these results indicate that catalytically inactive DIS3L2, characteristic of Perlman syndrome, can lead to deregulation of its target RNAs to disturb transcriptome homeostasis.
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PMID:Perlman syndrome nuclease DIS3L2 controls cytoplasmic non-coding RNAs and provides surveillance pathway for maturing snRNAs. 2743 25