Proofreading and spellchecking: A two-tier strategy for pre-mRNA splicing quality control

Egecioglu, Defne E.; Chanfreau, Guillaume

doi:10.1261/rna.2454711

Cited by 36 publications

(35 citation statements)

References 59 publications

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“…To prevent the accumulation of aberrant mRNAs (i.e., mRNAs that are erroneously or not completely spliced), eukaryotes have developed various quality control systems (Egecioglu and Chanfreau, 2011). Spliceosomal DExD/H box ATPases provide the first layer of defense.…”

Section: The Gldpa 59 Flanking Region: a Player In Posttranscriptionamentioning

confidence: 99%

“…Spliceosomal DExD/H box ATPases provide the first layer of defense. They act as kinetic proofreading systems and limit the escape of unspliced or erroneously spliced RNAs from the spliceosome (Egecioglu and Chanfreau, 2011). Despite the accuracy of these proofreading activities, unspliced mRNAs may escape detection; therefore, external quality control systems have been built up.…”

Section: The Gldpa 59 Flanking Region: a Player In Posttranscriptionamentioning

confidence: 99%

“…The nuclear exosome takes part in the degradation of unspliced RNAs (Houseley et al, 2006;Fasken and Corbett, 2009), although the molecular mechanisms by which unspliced RNAs are recognized are not yet clear. Exon-junction complexes that are deposited on spliced RNAs might be involved in the recognition mechanism (Egecioglu and Chanfreau, 2011). These protein complexes also play a prominent role in nonsense-mediated mRNA decay.…”

Section: The Gldpa 59 Flanking Region: a Player In Posttranscriptionamentioning

confidence: 99%

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Regulation of the Photorespiratory GLDPA Gene in C4 Flaveria: An Intricate Interplay of Transcriptional and Posttranscriptional Processes

et al. 2012

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The mitochondrial Gly decarboxylase complex (GDC) is a key component of the photorespiratory pathway that occurs in all photosynthetically active tissues of C 3 plants but is restricted to bundle sheath cells in C 4 species. GDC is also required for general cellular C 1 metabolism. In the Asteracean C 4 species Flaveria trinervia, a single functional GLDP gene, GLDPA, encodes the P-subunit of GDC, a decarboxylating Gly dehydrogenase. GLDPA promoter reporter gene fusion studies revealed that this promoter is active in bundle sheath cells and the vasculature of transgenic Flaveria bidentis (C 4 ) and the Brassicacean C 3 species Arabidopsis thaliana, suggesting the existence of an evolutionarily conserved gene regulatory system in the bundle sheath. Here, we demonstrate that GLDPA gene regulation is achieved by an intricate interplay of transcriptional and posttranscriptional mechanisms. The GLDPA promoter is composed of two tandem promoters, P R2 and P R7 , that together ensure a strong bundle sheath expression. While the proximal promoter (P R7 ) is active in the bundle sheath and vasculature, the distal promoter (P R2 ) drives uniform expression in all leaf chlorenchyma cells and the vasculature. An intron in the 59 untranslated leader of P R2 -derived transcripts is inefficiently spliced and apparently suppresses the output of P R2 by eliciting RNA decay.

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Section: The Gldpa 59 Flanking Region: a Player In Posttranscriptionamentioning

confidence: 99%

Section: The Gldpa 59 Flanking Region: a Player In Posttranscriptionamentioning

confidence: 99%

Section: The Gldpa 59 Flanking Region: a Player In Posttranscriptionamentioning

confidence: 99%

See 1 more Smart Citation

Regulation of the Photorespiratory GLDPA Gene in C4 Flaveria: An Intricate Interplay of Transcriptional and Posttranscriptional Processes

et al. 2012

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“…The spliceosome is responsible for pre-mRNA splicing and is composed of a large number of proteins and five small nuclear RNAs (snRNAs): U1, U2, U4, U5, and U6 (Wahl et al 2009;Egecioglu and Chanfreau 2011). At the heart of the spliceosome is the U2/U6 snRNA complex (Hausner et al 1990;Madhani et al 1990;Datta and Weiner 1991;Madhani and Guthrie 1992;Luukkonen and Seraphin 1998), an essential component of the active site of the spliceosome.…”

Section: Introductionmentioning

confidence: 99%

Structure of the yeast U2/U6 snRNA complex

Burke¹,

Sashital²,

Zuo³

et al. 2012

RNA

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The U2/U6 snRNA complex is a conserved and essential component of the active spliceosome that interacts with the pre-mRNA substrate and essential protein splicing factors to promote splicing catalysis. Here we have elucidated the solution structure of a 111-nucleotide U2/U6 complex using an approach that integrates SAXS, NMR, and molecular modeling. The U2/U6 structure contains a three-helix junction that forms an extended ''Y'' shape. The U6 internal stem-loop (ISL) forms a continuous stack with U2/U6 Helices Ib, Ia, and III. The coaxial stacking of Helix Ib on the U6 ISL is a configuration that is similar to the Domain V structure in group II introns. Interestingly, essential features of the complex-including the U80 metal binding site, AGC triad, and pre-mRNA recognition sites-localize to one face of the molecule. This observation suggests that the U2/U6 structure is well-suited for orienting substrate and cofactors during splicing catalysis.

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“…Several mechanisms are known to control the quality of RNAs in the nucleus (Sommer and Nehrbass 2005;Egecioglu and Chanfreau 2011). One such mechanism blocks the export of unspliced pre-mRNAs from the nucleus to the cytoplasm, thus preventing their translation into aberrant polypeptides (Chang and Sharp 1989;Legrain and Rosbash 1989).…”

mentioning

confidence: 99%

Coordinated regulation of neuronal mRNA steady-state levels through developmentally controlled intron retention

Yap¹,

Lim²,

Khandelia³

et al. 2012

Genes Dev.

260

295

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Differentiated cells acquire unique structural and functional traits through coordinated expression of lineagespecific genes. An extensive battery of genes encoding components of the synaptic transmission machinery and specialized cytoskeletal proteins is activated during neurogenesis, but the underlying regulation is not well understood. Here we show that genes encoding critical presynaptic proteins are transcribed at a detectable level in both neurons and nonneuronal cells. However, in nonneuronal cells, the splicing of 39-terminal introns within these genes is repressed by the polypyrimidine tract-binding protein (Ptbp1). This inhibits the export of incompletely spliced mRNAs to the cytoplasm and triggers their nuclear degradation. Clearance of these introncontaining transcripts occurs independently of the nonsense-mediated decay (NMD) pathway but requires components of the nuclear RNA surveillance machinery, including the nuclear pore-associated protein Tpr and the exosome complex. When Ptbp1 expression decreases during neuronal differentiation, the regulated introns are spliced out, thus allowing the accumulation of translation-competent mRNAs in the cytoplasm. We propose that this mechanism counters ectopic and precocious expression of functionally linked neuron-specific genes and ensures their coherent activation in the appropriate developmental context.

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Proofreading and spellchecking: A two-tier strategy for pre-mRNA splicing quality control

Cited by 36 publications

References 59 publications

Regulation of the Photorespiratory GLDPA Gene in C4 Flaveria: An Intricate Interplay of Transcriptional and Posttranscriptional Processes

Regulation of the Photorespiratory GLDPA Gene in C4 Flaveria: An Intricate Interplay of Transcriptional and Posttranscriptional Processes

Structure of the yeast U2/U6 snRNA complex

Coordinated regulation of neuronal mRNA steady-state levels through developmentally controlled intron retention

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