Premature termination codons do not affect the rate of splicing of neighboring introns

Lytle, J. Robin; Steitz, Joan A.

doi:10.1261/rna.5241404

Cited by 17 publications

(11 citation statements)

References 66 publications

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“…They showed that the size of the PTC+ focus was larger than that of the PTC− focus and suggested that this effect is due to PTC+ pre-mRNA accumulation at the site of transcription. However, we see no difference in focus size by FISH when examining single integrants of PTC+ and PTC− reporter genes in yeast, consistent with a PTC-independent explanation for this phenomenon (Lytle and Steitz 2004). Since there is also no observable PTC effect on nuclear-retained mRNAs by biochemical criteria, we conclude that the transcription-site foci of PTC− and PTC+ reporters are comparable.…”

Section: Discussionsupporting

confidence: 73%

“…In addition, other observations in mammalian systems have shown that a PTC can affect specific nuclear events, such as alternative splicing and 3 end formation (Brogna 1999;Wang et al 2002). Muhlemann and colleagues (2001) further demonstrated by fluorescent in situ hybridization (FISH) that pre-mRNAs accumulate in larger transcriptionsite foci from integrated PTC-containing reporter genes, although this interpretation has been recently questioned as being due to NMD-independent events (Lytle and Steitz 2004). Taken together, the results indicate that a PTC can affect features of RNA metabolism, within or associated with mammalian nuclei.…”

Section: Introductionmentioning

confidence: 99%

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Nonsense-mediated decay does not occur within the yeast nucleus

Kuperwasser

Brogna²,

Dower³

et al. 2004

RNA

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Nonsense-mediated decay (NMD) is a eukaryotic regulatory process that degrades mRNAs with premature termination codons (PTCs). Although NMD is a translation-dependent process, there is evidence from mammalian systems that PTC recognition and mRNA degradation takes place in association with nuclei. Consistent with this notion, degradation of mammalian PTC-containing mRNAs occurs when they are bound by the cap binding complex (CBC) during a "pioneer" round of translation. Moreover, there are reports indicating that a PTC can trigger other nuclear events such as alternative splicing, abnormal 3 end processing, and accumulation of pre-mRNA at transcription sites. To examine whether a PTC can elicit similar nuclear events in yeast, we used RNA export-defective mutants to sequester mRNAs within nuclei. The results indicate that nuclear PTCcontaining yeast RNAs are NMD insensitive. We also observed by fluorescent in situ hybridization that there was no PTC effect on mRNA accumulated at the site of transcription. Finally, we show that yeast NMD occurs minimally if at all on CBC-bound transcripts, arguing against a CBC-mediated pioneer round of translation in yeast. The data taken together indicate that there are no direct consequences of a PTC within the yeast nucleus.

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Section: Discussionsupporting

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Nonsense-mediated decay does not occur within the yeast nucleus

Kuperwasser

Brogna²,

Dower³

et al. 2004

RNA

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“…The RNase protection protocol was adapted from one published earlier (45) and is described in detail in SI Materials and Methods and elsewhere (51).…”

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confidence: 99%

Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5′ UTR as in the 3′ UTR

Lytle

Yario²,

Steitz³

2007

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

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In animals, microRNAs (miRNAs) bind to the 3 UTRs of their target mRNAs and interfere with translation, although the exact mechanism of inhibition of protein synthesis remains unclear. Functional miRNA-binding sites in the coding regions or 5 UTRs of endogenous mRNAs have not been identified. We studied the effect of introducing miRNA target sites into the 5 UTR of luciferase reporter mRNAs containing internal ribosome entry sites (IRESs), so that potential steric hindrance by a microribonucleoprotein complex would not interfere with the initiation of translation. In human HeLa cells, which express endogenous let-7a miRNA, the translational efficiency of these IRES-containing reporters with 5 let-7 complementary sites from the Caenorhabditis elegans lin-41 3 UTR was repressed. Similarly, the IRES-containing reporters were translationally repressed when human Ago2 was tethered to either the 5 or 3 UTR. Interestingly, the method of DNA transfection affected our ability to observe miRNA-mediated repression. Our results suggest that association with any position on a target mRNA is mechanistically sufficient for a microribonucleoprotein to exert repression of translation at some step downstream of initiation.internal ribosome entry sites ͉ repression ͉ method of transfection ͉ let-7 miRNP ͉ translation efficiency

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“…As splicing is a nuclear event -much of it occurring co-transcriptionally (see below) -this also implies that detection must take place close to the transcription site (Wilkinson and Shyu, 2002;Vasudevan and Peltz, 2003). However, recent work suggests that the effects may not be as large as originally suspected (Lytle and Steitz, 2004).…”

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confidence: 99%

The case for nuclear translation

Iborra

Jackson

Cook

2004

Journal of Cell Science

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Although it is frequently assumed that translation does not occur in eukaryotic nuclei, recent evidence suggests that some translation can take place and that it is closely coupled to transcription. The first evidence concerns the destruction of nuclear mRNAs containing premature termination codons by nonsense-mediated decay (NMD). Only ribosomes can detect termination codons, and as some NMD occurs within the nuclear fraction, active nuclear ribosomes could perform the required detection. The second evidence is the demonstration that tagged amino acids are incorporated into nascent polypeptides in a nuclear process coupled to transcription. The third evidence is that components involved in translation, NMD and transcription colocalize, coimmunoprecipitate and co-purify. All these results are simply explained if nuclear ribosomes scan nascent transcripts for premature termination codons at the site of transcription. Alternatively, the scanning needed for NMD might take place at the nuclear membrane, and contaminating cytoplasmic ribosomes might give the appearance of some nuclear translation. We argue, however, that the balance of evidence favours bona fide nuclear translation.

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Premature termination codons do not affect the rate of splicing of neighboring introns

Cited by 17 publications

References 66 publications

Nonsense-mediated decay does not occur within the yeast nucleus

Nonsense-mediated decay does not occur within the yeast nucleus

Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5′ UTR as in the 3′ UTR

The case for nuclear translation

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