Characterization of the biochemical properties of the human Upf1 gene product that is involved in nonsense-mediated mRNA decay

Bhattacharya, Anirban; Czaplinski, Kevin; Trifillis, Panayiota; He, Feng; Jacobson, Allan; Peltz, Stuart W.

doi:10.1017/s1355838200000546

Cited by 175 publications

(166 citation statements)

References 44 publications

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“…However, it should be noted that the assay used does not distinguish between differences in splicing efficiencies and differential stability of the resulting mRNA products. Both ZmHy2 IV/V 1 and IV/V 2 mRNAs are potential targets of the nonsensemediated decay pathway, a system characterized in yeast, invertebrates, mammals, and plants that functions to rapidly degrade mRNAs containing premature stop codons (Pulak and Anderson, 1993;Bhattacharya et al, 2000;Ruiz-Echevarria andPeltz, 2000, Isshiki et al, 2001). It is interesting to note that the observed frequencies of type 1, type 2, and type 3 splicing at intron IV are much more similar to each other in the elm1 background and are consistent with equal splicing at the three sites (chi-square test of observed against equal frequency at all sites; x 2 5 0.16, P .…”

Section: Discussionmentioning

confidence: 99%

TheElm1(ZmHy2) Gene of Maize Encodes a Phytochromobilin Synthase

et al. 2004

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The light insensitive maize (Zea mays) mutant elongated mesocotyl1 (elm1) has previously been shown to be deficient in the synthesis of the phytochrome chromophore 3E-phytochromobilin (PΦB). To identify the Elm1 gene, a maize homolog of the Arabidopsis PΦB synthase gene AtHY2 was isolated and designated ZmHy2. ZmHy2 encodes a 297-amino acid protein of 34 kD that is 50% identical to AtHY2. ZmHY2 was predicted to be plastid localized and was targeted to chloroplasts following transient expression in tobacco (Nicotiana plumbaginifolia) leaves. Molecular mapping indicated that ZmHy2 is a single copy gene in maize that is genetically linked to the Elm1 locus. Sequence analysis revealed that the ZmHy2 gene of elm1 mutants contains a single G to A transition at the 3′ splice junction of intron III resulting in missplicing and premature translational termination. However, flexibility in the splicing machinery allowed a small pool of in-frame ZmHy2 transcripts to accumulate in elm1 plants. In addition, multiple ZmHy2 transcript forms accumulated in both wild-type and elm1 mutant plants. ZmHy2 splice variants were expressed in Escherichia coli and products examined for activity using a coupled apophytochrome assembly assay. Only full-length ZmHY2 (as defined by homology to AtHY2) was found to exhibit PΦB synthase activity. Thus, the elm1 mutant of maize is deficient in phytochrome response due to a lesion in a gene encoding phytochromobilin synthase that severely compromises the PΦB pool.

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Section: Discussionmentioning

confidence: 99%

TheElm1(ZmHy2) Gene of Maize Encodes a Phytochromobilin Synthase

et al. 2004

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“…Human UPF1 is a 5'-3' DNA and RNA helicase with nucleic acid-dependent ATPase and ATP-dependent activities. 40,41 The C-terminal PIN domain of hEST1A exhibits an overall structure similar to ribonucleases of the RNase H family and displays single stranded RNA endonuclease activity under certain experimental conditions. 42 UPF1 and hEST1A mutants lacking specific enzymatic activities will be used to understand if UPF1-mediated unwinding and hEST1A-mediated cleavage of TERRA molecules play a role in TERRA displacement from chromatin.…”

Section: Terra Regulatory Pathwaysmentioning

confidence: 99%

Telomeres: The silence is broken

Azzalin¹,

Lingner²

2008

Cell Cycle

106

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“…This event marks the mRNA for degradation; however, at this point the commitment to the NMD pathway is thought to still be reversible. UPF1 is a group 1 RNA helicase, a nucleic acid-dependent ATPase, and a phosphorylation substrate of SMG1 kinase (Czaplinski et al 1995;Bhattacharya et al 2000;Yamashita et al 2001). Two other core NMD factors, 4 UPF2 and UPF3, are thought to promote SMG1-mediated phosphorylation of UPF1 (Kashima et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Autoregulation of the nonsense-mediated mRNA decay pathway in human cells

Yepiskoposyan¹,

Aeschimann²,

Nilsson³

et al. 2011

RNA

220

292

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Nonsense-mediated mRNA decay (NMD) is traditionally portrayed as a quality-control mechanism that degrades mRNAs with truncated open reading frames (ORFs). However, it is meanwhile clear that NMD also contributes to the post-transcriptional gene regulation of numerous physiological mRNAs. To identify endogenous NMD substrate mRNAs and analyze the features that render them sensitive to NMD, we performed transcriptome profiling of human cells depleted of the NMD factors UPF1, SMG6, or SMG7. It revealed that mRNAs up-regulated by NMD abrogation had a greater median 39-UTR length compared with that of the human mRNAome and were also enriched for 39-UTR introns and uORFs. Intriguingly, most mRNAs coding for NMD factors were among the NMD-sensitive transcripts, implying that the NMD process is autoregulated. These mRNAs all possess long 39 UTRs, and some of them harbor uORFs. Using reporter gene assays, we demonstrated that the long 39 UTRs of UPF1, SMG5, and SMG7 mRNAs are the main NMD-inducing features of these mRNAs, suggesting that long 39 UTRs might be a frequent trigger of NMD.

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Characterization of the biochemical properties of the human Upf1 gene product that is involved in nonsense-mediated mRNA decay

Abstract: ABSTRACT

Cited by 175 publications

References 44 publications

TheElm1(ZmHy2) Gene of Maize Encodes a Phytochromobilin Synthase

TheElm1(ZmHy2) Gene of Maize Encodes a Phytochromobilin Synthase

Telomeres: The silence is broken

Autoregulation of the nonsense-mediated mRNA decay pathway in human cells

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