Aberrant mRNAs with extended 3′ UTRs are substrates for rapid degradation by mRNA surveillance

Muhlrad, Denise; Parker, Roy

doi:10.1017/s1355838299990829

Cited by 211 publications

(169 citation statements)

References 34 publications

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“…Consistent with this model, the majority of yeast 39 UTRs are homogeneous in length and aberrant transcripts with exceptionally long 39 UTRs are substrates for NMD (Muhlrad and Parker 1999). In contrast, the requirement for a splicing-dependent signal seems to be a particular feature of mammalian NMD, and it is well established that EJCs play a pivotal role in the mechanism of PTC definition (Behm-Ansmant et al 2007).…”

Section: Discussionmentioning

confidence: 74%

Proximity of the poly(A)-binding protein to a premature termination codon inhibits mammalian nonsense-mediated mRNA decay

Silva

Ribeiro²,

Inácio³

et al. 2008

RNA

140

152

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mRNA surveillance pathways selectively clear defective mRNAs from the cell. As such, these pathways serve as important modifiers of genetic disorders. Nonsense-mediated decay (NMD), the most intensively studied surveillance pathway, recognizes mRNAs with premature termination codons (PTCs). In mammalian systems the location of a PTC more than 50 nucleotides 59 to the terminal exon-exon junction is a critical determinant of NMD. However, mRNAs with nonsense codons that fulfill this requirement but are located very early in the open reading frame can effectively evade NMD. The unexpected resistance of such mRNAs with AUG-proximal PTCs to accelerated decay suggests that important determinants of NMD remain to be identified. Here, we report that an NMD-sensitive mRNA can be stabilized by artificially tethering the cytoplasmic poly(A) binding protein 1, PABPC1, at a PTC-proximal position. Remarkably, the data further suggest that NMD of an mRNA with an AUG-proximal PTC can also be repressed by PABPC1, which might be brought into proximity with the PTC during cap-dependent translation and 43S scanning. These results reveal a novel parameter of NMD in mammalian cells that can account for the stability of mRNAs with AUG-proximal PTCs. These findings serve to expand current mechanistic models of NMD and mRNA translation.

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Section: Discussionmentioning

confidence: 74%

Proximity of the poly(A)-binding protein to a premature termination codon inhibits mammalian nonsense-mediated mRNA decay

Silva

Ribeiro²,

Inácio³

et al. 2008

RNA

140

152

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“…The extended 3' UTR length by the premature stop codon is longer, and the mRNA is more degraded [19].…”

Section: Discussionmentioning

confidence: 99%

Novel mutations of cholesteryl ester transfer protein (CETP) gene in Japanese hyperalphalipoproteinemic subjects

Ohtani

Inazu

Noji

et al. 2012

Clinica Chimica Acta

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Background: The half of hyperalphalipoproteinemia (HALP) in Japan is caused by CETP gene mutations. Other than two prevalent mutations (D442G and Intron 14 splicing donor site +1 G>A), some rare CETP mutations are found in Japanese HALP subjects.Methods: CETP gene analysis of genomic DNA from subjects was performed by restriction fragment length polymorphism (RFLP) and sequencing analysis. Mutations which were suspected to cause a splicing defect or a protein secretion defect were investigated in COS-1 cells transfected with a CETP minigene construct or a cDNA expression vector.Results: Each of three subjects was identified as a carrier of CETP gene mutation of a compound heterozygote of c.653_654delGGinsAAAC and Intron 14 splicing donor site +1 G>A, a heterozygote of c.658G>A or a homozygote of L261R. The c.658G>A mutation was located at the last nucleotide of exon 7, and it was confirmed to cause splicing abnormality revealed by the CETP minigene analysis. The L261R CETP was not secreted to conditioned media of the cells.Conclusions: Three novel CETP gene mutations are responsible for HALP by CETP deficiency. It is predicted that there are more rare CETP gene mutations in Japanese, and these multiple rare mutations alone or a combination with each of prevalent mutations responsible for mild-to-moderate or marked HALP, respectively.3

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“…Some studies perspicuously indicated that abnormal 3 UTR modified by deletion or mutation may induce a rapid degradation of the metallothionein mRNA (Muhlrad and Parker, 1999;Levadoux-Martin et al, 2001). Some previous studies demonstrated that a tandem repeat of a CACC could be essential for the transcript localization Nury et al, 2005).…”

Section: The Structural Analysis Of Metallothioneinmentioning

confidence: 99%

Characteristics, functions, and applications of metallothionein in aquatic vertebrates

Weichao

Mao

et al. 2014

Front. Mar. Sci.

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The documents on Metallothioneins (MTs) in aquatic creatures, especially focusing on their function as biomarkers in environmental monitoring programmes, are vast and increasing. There are, however, few papers to summary the physiological role of MTs in aquatic organisms especially on development. The multifaceted roles of MTs include involvement in homeostasis, protection against heavy metals and oxidant damages, and metabolic regulation, sequestration and/or redox control. In this paper, we have collected published information on MTs in aquatic organisms-pisces, amphibians, mammals, etc., and analyzed their function in these aquatic animals. MTs have four main functions in aquatic vertebrate. They are respectively bioaccumulation of toxic metals and detoxification, homeostatic regulation of metals, protection against oxidative stress and neuroprotective mechanism. MTs separate in different tissues and they have various distributions in different tissues of aquatic vertebrate, including liver, gills, kidney, testes, and brain. MTs can be induced by a variety of environmental and physiological factors, among which, heavy metals are the main kind of MTs inducers in aquatic vertebrate. Here we pay more attention on the essential metals copper (Cu) and zinc (Zn) and the non-essential metals cadmium (Cd), silver (Ag), lead (Pb), and mercury (Hg).

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Aberrant mRNAs with extended 3′ UTRs are substrates for rapid degradation by mRNA surveillance

Cited by 211 publications

References 34 publications

Proximity of the poly(A)-binding protein to a premature termination codon inhibits mammalian nonsense-mediated mRNA decay

Proximity of the poly(A)-binding protein to a premature termination codon inhibits mammalian nonsense-mediated mRNA decay

Novel mutations of cholesteryl ester transfer protein (CETP) gene in Japanese hyperalphalipoproteinemic subjects

Characteristics, functions, and applications of metallothionein in aquatic vertebrates

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