A GC-rich sequence feature in the 3′ UTR directs UPF1-dependent mRNA decay in mammalian cells

Imamachi, Naoto; Salam, Kazi Abdus; Suzuki, Yutaka; Akimitsu, Nobuyoshi

doi:10.1101/gr.206060.116

Cited by 66 publications

(84 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Earlier studies demonstrated that UPF1 targets transcripts with GC-rich 3= UTRs (9,10), and both U1D and p26 were identified as preferentially protected transcripts with GC-rich 3= UTRs in the present study ( Fig. 5B).…”

Section: Discussionsupporting

confidence: 76%

“…EJC-independent NMD occurs when UPF1 bound to the 3= untranslated region (UTR) interacts with eukaryotic release factor 3 (eRF3), which is associated with a terminating ribosome, leading to phosphorylation of UPF1 (2). While UPF1 can bind to any accessible RNA, binding is enriched in transcripts that are GC rich (Ͼ15% increased GC content compared to average) (9,10), as well as in transcripts with long 3= UTRs (Ͼ1.5-fold-greater length than average) (11,12).…”

mentioning

confidence: 99%

See 1 more Smart Citation

The Multifunctional Long-Distance Movement Protein of Pea Enation Mosaic Virus 2 Protects Viral and Host Transcripts from Nonsense-Mediated Decay

May

Johnson

Ilyas

et al. 2020

mBio

View full text Add to dashboard Cite

The nonsense-mediated decay (NMD) pathway presents a challenge for RNA viruses with termination codons that precede extended 3= untranslated regions (UTRs). The umbravirus Pea enation mosaic virus 2 (PEMV2) is a nonsegmented, positive-sense RNA virus with an unusually long 3= UTR that is susceptible to NMD. To establish a systemic infection, the PEMV2 long-distance movement protein p26 was previously shown to both stabilize viral RNAs and bind them for transport through the plant's vascular system. The current study demonstrated that p26 protects both viral and nonviral messenger RNAs from NMD. Although p26 localizes to both the cytoplasm and nucleolus, p26 exerts its anti-NMD effects exclusively in the cytoplasm independently of long-distance movement. Using a transcriptome-wide approach in the model plant Nicotiana benthamiana, p26 protected a subset of cellular NMD target transcripts, particularly those containing long, structured, GC-rich 3= UTRs. Furthermore, transcriptome sequencing (RNA-seq) revealed that the NMD pathway is highly dysfunctional during PEMV2 infection, with 1,820 (48%) of NMD targets increasing in abundance. Widespread changes in the host transcriptome are common during plant RNA virus infections, and these results suggest that, in at least some instances, virus-mediated NMD inhibition may be a major contributing factor. IMPORTANCE Nonsense-mediated decay (NMD) represents an RNA regulatory pathway that degrades both natural and faulty messenger RNAs with long 3= untranslated regions. NMD targets diverse families of RNA viruses, requiring that viruses counteract the NMD pathway for successful amplification in host cells. A protein required for long-distance movement of Pea enation mosaic virus 2 (PEMV2) is shown to also protect both viral and host mRNAs from NMD. RNA-seq analyses of the Nicotiana benthamiana transcriptome revealed that PEMV2 infection significantly impairs the host NMD pathway. RNA viruses routinely induce large-scale changes in host gene expression, and, like PEMV2, may use NMD inhibition to alter the host transcriptome in an effort to increase virus amplification.

show abstract

Section: Discussionsupporting

confidence: 76%

mentioning

confidence: 99%

The Multifunctional Long-Distance Movement Protein of Pea Enation Mosaic Virus 2 Protects Viral and Host Transcripts from Nonsense-Mediated Decay

May

Johnson

Ilyas

et al. 2020

mBio

View full text Add to dashboard Cite

show abstract

“…It is tempting to propose rather that, by unwinding GC-rich double-stranded regions over the entire length of the mRNA, DDX6 facilitates XRN1 progression. UPF1, another RNA helicase involved in mRNA decay, has also been shown to preferentially affect the decay of GC-rich mRNAs [49]. The same observation was made for targets of the NMD pathway, which involves UPF1, SMG6 and SMG7 [50].…”

Section: Distinct Decay Pathwaysmentioning

confidence: 66%

GC content shapes mRNA decay and storage in human cells

Courel

Clément

Foretek

et al. 2018

Preprint

View full text Add to dashboard Cite

Control of protein expression results from the fine tuning of mRNA synthesis, decay and translation. These processes, which are controlled by a large number of RNA-binding proteins and by localization in RNP granules such as P-bodies, appear often intimately linked although the rules of this interplay are not well understood. In this study, we combined our recent P-body transcriptome with various transcriptomes obtained following silencing of broadly acting mRNA decay and repression factors. This analysis revealed the central role of GC content in mRNA fate, in terms of P-body localization, mRNA translation and mRNA decay. It also rationalized why PBs mRNAs have a strikingly low protein yield. We report too the existence of distinct mRNA decay pathways with preference for AU-rich or GC-rich transcripts. Compared to this impact of the GC content, sequence-specific RBPs and miRNAs appeared to have only modest additional effects on their bulk targets. Altogether, these results lead to an integrated view of post-transcriptional control in human cells where most regulation at the level of translation is dedicated to AU-rich mRNAs, which have a limiting protein yield, whereas regulation at the level of 5' decay applies to GC-rich mRNAs, whose translation is optimal.

show abstract

“…BRIC-seq enables the determination of genome-wide RNA stability by monitoring the decrease in BrU-labeled RNA abundance over time from which the RNA half-life of each transcript is calculated. By comparing the half-lives of transcripts in control cells with the halflives of those in PUM-depleted cells, we can identify mRNAs of which stability is regulated by PUMs 11 . Combining the results of the RIP-seq and BRIC-seq analyses yields the targets of PUMs ( Figure 1A).…”

Section: Identification Of Target Mrnas Of Human Pum1 and Pum2 By Ripmentioning

confidence: 99%

“…For the RBPs involved in mRNA decay, not all mRNAs that bind the RBP are targets of degradation. For instance, only subset of the mRNAs that bind to UPF1, an RBP involved in the RNA degradation and RNA quality control, is subject to UPF1-dependent mRNA degradation 11 . Consequently, knowledge of the mRNAs that bind an RBP is insufficient.…”

Section: Introductionmentioning

confidence: 99%

Systematic Analysis of Targets of Pumilio (PUM)-Mediated mRNA Decay Identifies a Role of PUM1 in Regulating DNA Damage Response Pathway

Yamada

Imamachi

Imamura

et al. 2018

Preprint

Self Cite

View full text Add to dashboard Cite

RNA-binding proteins (RBPs) play a pivotal role in gene expression by modulating the stability of transcripts; however, the identification of degradation targets of RBPs remains difficult. Here, we identified 48 target mRNAs of human Pumilio 1 (PUM1), an evolutionally conserved RBP, by combined analysis of transcriptome-wide mRNA stabilities and the binding of mRNAs to PUM1. Here, we developed an approach to identify mRNA targets of Pumilio 1 (PUM1), an evolutionally conserved RBP. By combined analysis of transcriptome-wide mRNA stabilities and the binding of mRNAs to PUM1, we identified 48 mRNAs that both bound to PUM1 and exhibited PUM1-dependent degradation. Analysis of changes in the abundance of PUM1 and its targets in RNA-seq data indicated that DNA-damaging agents negatively regulated PUM1-mediated mRNA decay. Cells exposed to cisplatin had reduced PUM1 abundance and increased PCNA and UBE2A mRNAs, encoding proteins involved in DNA repair by translesion synthesis (TLS). Cells overexpressing PUM1 exhibited impaired DNA synthesis and TLS and increased sensitivity to the cytotoxic effect of cisplatin. Thus, our method identified targets of PUM1-mediated decay and revealed that cells respond to DNA damage by inhibiting PUM1-mediated mRNA decay to activate TLS.

show abstract

A GC-rich sequence feature in the 3′ UTR directs UPF1-dependent mRNA decay in mammalian cells

Cited by 66 publications

References 48 publications

The Multifunctional Long-Distance Movement Protein of Pea Enation Mosaic Virus 2 Protects Viral and Host Transcripts from Nonsense-Mediated Decay

The Multifunctional Long-Distance Movement Protein of Pea Enation Mosaic Virus 2 Protects Viral and Host Transcripts from Nonsense-Mediated Decay

GC content shapes mRNA decay and storage in human cells

Systematic Analysis of Targets of Pumilio (PUM)-Mediated mRNA Decay Identifies a Role of PUM1 in Regulating DNA Damage Response Pathway

Contact Info

Product

Resources

About