A programmed -1 ribosomal frameshift signal can function as a cis-acting mRNA destabilizing element

Plant, Ewan P.; Wang, Pinger; Jacobs, Jonathan L.; Dinman, Jonathan D.

doi:10.1093/nar/gkh256

Cited by 43 publications

(37 citation statements)

References 32 publications

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“…Similarly, it has been proposed that in mammalian cells, NMD occurs only during a pioneer round of translation (Lejeune et al 2004). In contrast, studies in both yeast and rats have shown a decrease in RNA levels due to an infrequently translated PTC (Buzina and Shulman 1999;Plant et al 2004). This is not surprising since RNAs in yeast can undergo NMD during any round of translation (Maderazo et al 2003).…”

Section: Possible Nmd Mechanisms For Rsv Rnamentioning

confidence: 98%

A 3′ UTR sequence stabilizes termination codons in the unspliced RNA of Rous sarcoma virus

Weil

Beemon²

2005

RNA

106

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Eukaryotic cells target mRNAs to the nonsense-mediated mRNA decay (NMD) pathway when translation terminates within the coding region. In mammalian cells, this is presumably due to a downstream signal deposited during pre-mRNA splicing. In contrast, unspliced retroviral RNA undergoes NMD in chicken cells when premature termination codons (PTCs) are present in the gag gene. Surprisingly, deletion of a 401-nt 3¢ UTR sequence immediately downstream of the normal gag termination codon caused this termination event to be recognized as premature. We termed this 3¢ UTR region the Rous sarcoma virus (RSV) stability element (RSE). The RSE also stabilized the viral RNA when placed immediately downstream of a PTC in the gag gene. Deletion analysis of the RSE indicated a smaller functional element. We conclude that this 3¢ UTR sequence stabilizes termination codons in the RSV RNA, and termination codons not associated with such an RSE sequence undergo NMD.

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Section: Possible Nmd Mechanisms For Rsv Rnamentioning

confidence: 98%

A 3′ UTR sequence stabilizes termination codons in the unspliced RNA of Rous sarcoma virus

Weil

Beemon²

2005

RNA

106

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“…If a uORF (upstream ORF) is translated by the ribosome, its TC could be regarded as premature due to the bulk of the downstream sequences that separate stop codon position from poly(A) tail as well as due to possible downstream intron(s). Furthermore, programmed frameshifts, selenocysteineencoding UGA codons, and leaky scanning initiation codons can target transcripts for NMD (Moriarty et al 1998;Welch and Jacobson 1999;Plant et al 2004). …”

Section: Introductionmentioning

confidence: 99%

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

Yepiskoposyan¹,

Aeschimann²,

Nilsson³

et al. 2011

RNA

219

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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“…Although it is relatively rare, Ϫ1 PRF has also been documented to occur in prokaryotes (Escherichia coli dnaX gene), with just one instance of Ϫ1 PRF clearly shown to occur in mammalian cells (Edr gene) (12). Recent findings suggest that Ϫ1 PRF might be used in Saccharomyces cerevisiae to endogenously posttranscriptionally regulate gene expression by targeting mRNAs containing premature termination codons for nonsensemediated mRNA decay (13).…”

mentioning

confidence: 99%

A loop 2 cytidine-stem 1 minor groove interaction as a positive determinant for pseudoknot-stimulated –1 ribosomal frameshifting

Cornish

Hennig

Giedroc

2005

Proc. Natl. Acad. Sci. U.S.A.

170

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The molecular determinants of stimulation of ؊1 programmed ribosomal frameshifting (؊1 PRF) by RNA pseudoknots are poorly understood. Sugarcane yellow leaf virus (ScYLV) encodes a 28-nt mRNA pseudoknot that promotes ؊1 PRF between the P1 (protease) and P2 (polymerase) genes in plant luteoviruses. The solution structure of the ScYLV pseudoknot reveals a well ordered loop 2 (L2) that exhibits continuous stacking of A20 through C27 in the minor groove of the upper stem 1 (S1), with C25 flipped out of the triple-stranded stack. Five consecutive triple base pairs flank the helical junction where the 3 nucleotide of L2, C27, adopts a cytidine 27 N3-cytidine 14 2 -OH hydrogen bonding interaction with the C14-G7 base pair. This interaction is isosteric with the adenosine N1-2 -OH interaction in the related mRNA from beet western yellows virus (BWYV); however, the ScYLV and BWYV mRNA structures differ in their detailed L2-S1 hydrogen bonding and L2 stacking interactions. Functional analyses of ScYLV͞BWYV chimeric pseudoknots reveal that the ScYLV RNA stimulates a higher level of ؊1 PRF (15 ؎ 2%) relative to the BWYV pseudoknot (6 ؎ 1%), a difference traced largely to the identity of the 3 nucleotide of L2 (C27 vs. A25 in BWYV). Strikingly, C27A ScYLV RNA is a poor frameshift stimulator (2.0%) and is destabilized by Ϸ1.5 kcal⅐mol ؊1 (pH 7.0, 37°C) with respect to the wild-type pseudoknot. These studies establish that the precise network of weak interactions nearest the helical junction in structurally similar pseudoknots make an important contribution to setting the frameshift efficiency in mRNAs.base triple ͉ RNA pseudoknot ͉ translational recoding

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A programmed -1 ribosomal frameshift signal can function as a cis-acting mRNA destabilizing element

Cited by 43 publications

References 32 publications

A 3′ UTR sequence stabilizes termination codons in the unspliced RNA of Rous sarcoma virus

A 3′ UTR sequence stabilizes termination codons in the unspliced RNA of Rous sarcoma virus

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

A loop 2 cytidine-stem 1 minor groove interaction as a positive determinant for pseudoknot-stimulated –1 ribosomal frameshifting

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