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

Pirouz, Mehdi; Du, Peng; Munafò, Marzia; Gregory, Richard I.

doi:10.1016/j.celrep.2016.07.025

Cited by 72 publications

(167 citation statements)

References 60 publications

(79 reference statements)

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“…In contrast, DIS3 knockdown led to a decrease in Y RNA levels (ϳ30% for Y1 and ϳ20% for Y3) and DIS3L2 knockdown had no significant effect on Y RNA levels. This is in contrast to recent reports that suggest that DIS3L2 targets 3=-uridylated Y RNAs for degradation (36,37), although as discussed below, we found that only a small fraction of Y RNAs are uridylated in HeLa cells. Moreover, DIS3L coknockdown with PARN is sufficient to rescue Y RNA levels to control, suggesting that DIS3L is responsible for Y RNA degradation when PARN is limiting (Fig.…”

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confidence: 55%

PARN Modulates Y RNA Stability and Its 3′-End Formation

Shukla

Parker

2017

Molecular and Cellular Biology

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Loss-of-function mutations in 3=-to-5= exoribonucleases have been implicated in hereditary human diseases. For example, PARN mutations cause a severe form of dyskeratosis congenita (DC), wherein PARN deficiency leads to human telomerase RNA instability. Since the DC phenotype in PARN patients is even more severe than that of loss-of-function alleles in telomerase components, we hypothesized that PARN would also be required for the stability of other RNAs. Here, we show that PARN depletion reduces the levels of abundant human Y RNAs, which might contribute to the severe phenotype of DC observed in patients. Depletion of PAPD5 or the cytoplasmic exonuclease DIS3L rescues the effect of PARN depletion on Y RNA levels, suggesting that PARN stabilizes Y RNAs by removing oligoadenylated tails added by PAPD5, which would otherwise recruit DIS3L for Y RNA degradation. Through deep sequencing of 3= ends, we provide evidence that PARN can also deadenylate the U6 and RMRP RNAs without affecting their levels. Moreover, we observed widespread posttranscriptional oligoadenylation, uridylation, and guanylation of U6 and Y RNA 3= ends, suggesting that in mammalian cells, the formation of a 3= end for noncoding RNAs can be a complex process governed by the activities of various 3=-end polymerases and exonucleases.

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contrasting

confidence: 55%

PARN Modulates Y RNA Stability and Its 3′-End Formation

Shukla

Parker

2017

Molecular and Cellular Biology

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“…Interestingly, many ncRNAs are protected from this degradation by structures such as stem loops (X. Liu et al, ). These studies suggest that mRNA decay is important for making sure the death program passes the “point of no return.” In non‐apoptotic cells, this pathway of TUTases and DIS3L2 act in quality control pathways of mRNAs and ncRNAs (Pirouz, Du, Munafò, & Gregory, ; Ustianenko et al, ). In contrast to the destabilizing effect of terminal uridyl, a more recent report has identified promiscuous nucleotidyl transferase activity leading to guanylation of the poly(A) tail that protects mRNAs from degradation (Chang et al, ; Y. Lim et al, ).…”

Section: Non‐polyadenylate 3′ End Modifications and Epitranscriptomicsmentioning

confidence: 99%

Connections between 3′ end processing and DNA damage response: Ten years later

Murphy

Kleiman

2019

WIREs RNA

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Ten years ago we reviewed how the cellular DNA damage response (DDR) is controlled by changes in the functional and structural properties of nuclear proteins, resulting in a timely coordinated control of gene expression that allows DNA repair. Expression of genes that play a role in DDR is regulated not only at transcriptional level during mRNA biosynthesis but also by changing steady‐state levels due to turnover of the transcripts. The 3′ end processing machinery, which is important in the regulation of mRNA stability, is involved in these gene‐specific responses to DNA damage. Here, we review the latest mechanistic connections described between 3′ end processing and DDR, with a special emphasis on alternative polyadenylation, microRNA and RNA binding proteins‐mediated deadenylation, and discuss the implications of deregulation of these steps in DDR and human disease. This article is categorized under: RNA Processing > 3′ End Processing RNA‐Based Catalysis > Miscellaneous RNA‐Catalyzed Reactions RNA in Disease and Development > RNA in Disease

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“…Uridylation‐mediated RNA degradation is definitely among the crucial functions of uridylation. Notably, a uridylation‐ and Dis3L2‐mediated surveillance pathway is key for the degradation of defective noncoding RNAs . Uridylated misprocessed transcripts were also detected in human mitochondria raising the possibility that uridylated‐mediated RNA surveillance might also operate in this organelle .…”

Section: Resultsmentioning

confidence: 99%

“…As Pol III terminates transcription following the synthesis of a short stretch of uridines, unprocessed transcripts may be targeted directly by Dis3L2 after export to the cytosol. However, TUT4/7 definitely assists Dis3L2 mediated‐degradation by synthesizing short oligouridine tails, mostly at positions close to stable secondary structures (Figure (e)) . An elegant experiment based on the decay rate analysis of randomized terminal sequences confirmed that a short stretch of terminal uridines significantly enhances degradation by the Drosophila Dis3L2 …”

Section: Uridylation Represses the Mirtron Pathwaymentioning

confidence: 93%

“…4,41 Dis3L2 acts independently of the exosome and degrades a variety of RNA substrates in the cytosol, ranging from mRNAs to a range of noncoding RNAs including small RNAs. 34, [41][42][43]45,[79][80][81] Of note, uridylation favors Dis3L2-mediated decay. Determination of the structure of mouse Dis3L2 in complex with an oligo(U) RNA revealed extensive uracil-specific interactions, explaining how Dis3L2 preferentially recognizes uridylated RNA substrates.…”

Section: Boxmentioning

confidence: 99%

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RNA uridylation: a key posttranscriptional modification shaping the coding and noncoding transcriptome

et al. 2017

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RNA uridylation is a potent and widespread posttranscriptional regulator of gene expression. RNA uridylation has been detected in a range of eukaryotes including trypanosomes, animals, plants, and fungi, but with the noticeable exception of budding yeast. Virtually all classes of eukaryotic RNAs can be uridylated and uridylation can also tag viral RNAs. The untemplated addition of a few uridines at the 3 0 end of a transcript can have a decisive impact on RNA's fate. In rare instances, uridylation is an intrinsic step in the maturation of noncoding RNAs like for the U6 spliceosomal RNA or mitochondrial guide RNAs in trypanosomes. Uridylation can also switch specific miRNA precursors from a degradative to a processing mode. This switch depends on the number of uridines added which is regulated by the cellular context. Yet, the typical consequence of uridylation on mature noncoding RNAs or their precursors is to accelerate decay. Importantly, mRNAs are also tagged by uridylation. In fact, the advent of novel high throughput sequencing protocols has recently revealed the pervasiveness of mRNA uridylation, from plants to humans. As for noncoding RNAs, the main function to date for mRNA uridylation is to promote degradation. Yet, additional roles begin to be ascribed to U-tailing such as the control of mRNA deadenylation, translation control and possibly storage. All these new findings illustrate that we are just beginning to appreciate the diversity of roles played by RNA uridylation and its full temporal and spatial implication in regulating gene expression.

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

Cited by 72 publications

References 60 publications

PARN Modulates Y RNA Stability and Its 3′-End Formation

PARN Modulates Y RNA Stability and Its 3′-End Formation

Connections between 3′ end processing and DNA damage response: Ten years later

RNA uridylation: a key posttranscriptional modification shaping the coding and noncoding transcriptome

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