An intron proximal to a PTC enhances NMD in<i>Saccharomyces cerevisiae</i>

Wen, Jikai; He, Muyang; Petrić, Marija; Marzi, Laetitia; Wang, Jianming; Piechocki, Kim; McLeod, Tina; Singh, Anand Kumar; Dwivedi, Vibha

doi:10.1101/149245

Cited by 7 publications

(9 citation statements)

References 65 publications

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“…Furthermore, these data re-prompt questioning the fields' communally accepted syllogism that transcripts whose levels are increased in Upf1 depleted cells are therefore likely to be NMD targets. This might not always be a valid explanation: it has previously been argued that only a fraction of these increases might actually be a direct consequence of cytoplasmic mRNA stabilisation (Brogna et al, 2016;Brogna and Wen, 2009;Wen and Brogna, 2010;Wen et al, 2020). Here we have shown that there is overlap between genes associated with Upf1 and genes that have increased mRNA levels in upf1D.…”

Section: Discussionmentioning

confidence: 59%

Genome-wide chromosomal association of Upf1 is linked to Pol II transcription inSchizosaccharomyces pombe

Dwivedi

Wang

et al. 2021

Preprint

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Although the RNA helicase Upf1 has hitherto been examined mostly in relation to its cytoplasmic role in nonsense mediated mRNA decay (NMD), here we report high-throughput ChIP data indicating genome-wide association of Upf1 with active genes in Schizosaccharomyces pombe. This association is RNase sensitive and it correlates with Pol II transcription and mRNA expression levels. While changes in Pol II occupancy were detected at only some genes in a Upf1-deficient (upf1Δ strain, there is an increased Ser2 Pol II signal at all highly transcribed genes examined by ChIP-qPCR. Furthermore, upf1Δ cells are hypersensitive to the transcription elongation inhibitor 6-azauracil and display Pol II abnormalities suggestive of Pol II hyperphosphorylation. A significant proportion of the genes associated with Upf1 in wild-type conditions are also mis-regulated in upf1Δ. These data envisage that by operating on the nascent transcript Upf1 might influence Pol II phosphorylation and transcription.

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Section: Discussionmentioning

confidence: 59%

Genome-wide chromosomal association of Upf1 is linked to Pol II transcription inSchizosaccharomyces pombe

Dwivedi

Wang

et al. 2021

Preprint

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“…Therefore, EJCs can directly promote activation of NMD, exemplifying how nuclear splicing events communicate with cytoplasmic pathways through RNA-binding proteins for quality control. Interestingly, a recent study in yeast suggested that, despite lacking proteins homologous to EJC core components, an intron in proximity to a PTC enhances NMD [75]. This supports the possibility that a connection between splicing and NMD might be conserved from simple eukaryotic species.…”

Section: Further Surveillance In the Cytoplasm-detection Of Errors Via Nonsense-mediated Decaymentioning

confidence: 78%

Nuclear mRNA Quality Control and Cytoplasmic NMD Are Linked by the Guard Proteins Gbp2 and Hrb1

Krebber

2021

IJMS

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Pre-mRNA splicing is critical for cells, as defects in this process can lead to altered open reading frames and defective proteins, potentially causing neurodegenerative diseases and cancer. Introns are removed in the nucleus and splicing is documented by the addition of exon-junction-complexes (EJCs) at exon-exon boundaries. This “memory” of splicing events is important for the ribosome, which translates the RNAs in the cytoplasm. In case a stop codon was detected before an EJC, translation is blocked and the RNA is eliminated by the nonsense-mediated decay (NMD). In the model organism Saccharomyces cerevisiae, two guard proteins, Gbp2 and Hrb1, have been identified as nuclear quality control factors for splicing. In their absence, intron-containing mRNAs leak into the cytoplasm. Their presence retains transcripts until the process is completed and they release the mRNAs by recruitment of the export factor Mex67. On transcripts that experience splicing problems, these guard proteins recruit the nuclear RNA degradation machinery. Interestingly, they continue their quality control function on exported transcripts. They support NMD by inhibiting translation and recruiting the cytoplasmic degradation factors. In this way, they link the nuclear and cytoplasmic quality control systems. These discoveries are also intriguing for humans, as homologues of these guard proteins are present also in multicellular organisms. Here, we provide an overview of the quality control mechanisms of pre-mRNA splicing, and present Gbp2 and Hrb1, as well as their human counterparts, as important players in these pathways.

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“…Therefore, the main function of the EJC in NMD may be to increase the local concentration of such proteins [ 8 ]. The NMD-promoting function of the EJC has been further challenged by the discovery that in Schizosaccharomyces pombe and S. cerevisiae , splicing both upstream and downstream of PTCs enhances NMD, but is independent of EJC components [ 163 , 164 ]. Similarly, according to a recent report, the number of introns determine NMD efficiency in mammalian cells regardless of their position upstream or downstream of a PTC [ 112 ].…”

Section: Are There Any Indispensable Trans -Acmentioning

confidence: 99%

UPF1-Mediated RNA Decay—Danse Macabre in a Cloud

Lavysh

Neu‐Yilik

2020

Biomolecules

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Nonsense-mediated RNA decay (NMD) is the prototype example of a whole family of RNA decay pathways that unfold around a common central effector protein called UPF1. While NMD in yeast appears to be a linear pathway, NMD in higher eukaryotes is a multifaceted phenomenon with high variability with respect to substrate RNAs, degradation efficiency, effector proteins and decay-triggering RNA features. Despite increasing knowledge of the mechanistic details, it seems ever more difficult to define NMD and to clearly distinguish it from a growing list of other UPF1-mediated RNA decay pathways (UMDs). With a focus on mammalian NMD, we here critically examine the prevailing NMD models and the gaps and inconsistencies in these models. By exploring the minimal requirements for NMD and other UMDs, we try to elucidate whether they are separate and definable pathways, or rather variations of the same phenomenon. Finally, we suggest that the operating principle of the UPF1-mediated decay family could be considered similar to that of a computing cloud providing a flexible infrastructure with rapid elasticity and dynamic access according to specific user needs.

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An intron proximal to a PTC enhances NMD inSaccharomyces cerevisiae

Cited by 7 publications

References 65 publications

Genome-wide chromosomal association of Upf1 is linked to Pol II transcription inSchizosaccharomyces pombe

Genome-wide chromosomal association of Upf1 is linked to Pol II transcription inSchizosaccharomyces pombe

Nuclear mRNA Quality Control and Cytoplasmic NMD Are Linked by the Guard Proteins Gbp2 and Hrb1

UPF1-Mediated RNA Decay—Danse Macabre in a Cloud

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