Search results for "RNA decay"
showing 10 items of 16 documents
NMD-Based Gene Regulation—A Strategy for Fitness Enhancement in Plants?
2019
Abstract Post-transcriptional RNA quality control is a vital issue for all eukaryotes to secure accurate gene expression, both on a qualitative and quantitative level. Among the different mechanisms, nonsense-mediated mRNA decay (NMD) is an essential surveillance system that triggers degradation of both aberrant and physiological transcripts. By targeting a substantial fraction of all transcripts for degradation, including many alternative splicing variants, NMD has a major impact on shaping transcriptomes. Recent progress on the transcriptome-wide profiling and physiological analyses of NMD-deficient plant mutants revealed crucial roles for NMD in gene regulation and environmental response…
Multifactorial and Species-Specific Feedback Regulation of the RNA Surveillance Pathway Nonsense-Mediated Decay in Plants
2018
Abstract Nonsense-mediated decay (NMD) is an RNA surveillance mechanism that detects aberrant transcript features and triggers degradation of erroneous as well as physiological RNAs. Originally considered to be constitutive, NMD is now recognized to be tightly controlled in response to inherent signals and diverse stresses. To gain a better understanding of NMD regulation and its functional implications, we systematically examined feedback control of the central NMD components in two dicot and one monocot species. On the basis of the analysis of transcript features, turnover rates and steady-state levels, up-frameshift (UPF) 1, UPF3 and suppressor of morphological defects on genitalia (SMG)…
RNA uridylation and decay in plants
2018
RNA uridylation consists of the untemplated addition of uridines at the 3′ extremity of an RNA molecule. RNA uridylation is catalysed by terminal uridylyltransferases (TUTases), which form a subgroup of the terminal nucleotidyltransferase family, to which poly(A) polymerases also belong. The key role of RNA uridylation is to regulate RNA degradation in a variety of eukaryotes, including fission yeast, plants and animals. In plants, RNA uridylation has been mostly studied in two model species, the green algae Chlamydomonas reinhardtii and the flowering plant Arabidopsis thaliana . Plant TUTases target a variety of RNA substrates, differing in size and function. These RNA substrates include …
Caffeine boosts Ataluren's readthrough activity
2019
Abstract The readthrough of nonsense mutations by small molecules like Ataluren is considered a novel therapeutic approach to overcome the gene defect in several genetic diseases as cystic fibrosis (CF). This pharmacological approach suppresses translation termination at premature termination codons (PTCs readthrough) thus restoring the expression of a functional protein. However, readthrough might be limited by the nonsense-mediated mRNA decay (NMD), a cell process that reduces the amount/level of PTCs containing mRNAs. Here we investigate the combined action of Ataluren and caffeine to enhance the readthrough of PTCs. IB3.1 CF cells with a nonsense mutation were treated with caffeine to a…
Post-Transcriptional Regulation of Iron Homeostasis in Saccharomyces cerevisiae
2013
Iron is an essential micronutrient for all eukaryotic organisms because it participates as a redox cofactor in a wide variety of biological processes. Recent studies in Saccharomyces cerevisiae have shown that in response to iron deficiency, an RNA-binding protein denoted Cth2 coordinates a global metabolic rearrangement that aims to optimize iron utilization. The Cth2 protein contains two Cx8Cx5Cx3H tandem zinc fingers (TZFs) that specifically bind to adenosine/uridine-rich elements within the 3' untranslated region of many mRNAs to promote their degradation. The Cth2 protein shuttles between the nucleus and the cytoplasm. Once inside the nucleus, Cth2 binds target mRNAs and stimulate…
Regulation of human inducible nitric oxide synthase expression by an upstream open reading frame.
2019
Abstract The human inducible nitric oxide synthase (iNOS) gene contains an upstream open reading frame (uORF) in its 5′-untranslated region (5′-UTR) implying a translational regulation of iNOS expression. Transfection experiments in human DLD-1 cells revealed that the uORF although translatable seems not to inhibit the translation start at the bona fide ATG. Our data clearly show that human iNOS translation is cap-dependent and that the 5′-UTR of the iNOS mRNA contains no internal ribosome entry site. Translation of the bona fide coding sequence is most likely mediated by a leaky scanning mechanism. The 5′-UTR is encoded by exon 1 and exon 2 of the iNOS gene with the uORF stop codon located…
Nucleo-cytoplasmic shuttling of RNA-binding factors: mRNA buffering and beyond.
2022
Gene expression is a highly regulated process that adapts RNAs and proteins content to the cellular context. Under steady-state conditions, mRNA homeostasis is robustly maintained by tight controls that act on both nuclear transcription and cytoplasmic mRNA stability. In recent years, it has been revealed that several RNA-binding proteins (RBPs) that perform functions in mRNA decay can move to the nucleus and regulate transcription. The RBPs involved in transcription can also travel to the cytoplasm and regulate mRNA degradation and/or translation. The multifaceted functions of these shuttling nucleo-cytoplasm RBPs have raised the possibility that they can act as mRNA metabolism coordinator…
Nonsense-mediated mRNA decay controls the changes in yeast ribosomal protein pre-mRNAs levels upon osmotic stress.
2013
The expression of ribosomal protein (RP) genes requires a substantial part of cellular transcription, processing and translation resources. Thus, the RP expression must be tightly regulated in response to conditions that compromise cell survival. In Saccharomyces cerevisiae cells, regulation of the RP gene expression at the transcriptional, mature mRNA stability and translational levels during the response to osmotic stress has been reported. Reprogramming global protein synthesis upon osmotic shock includes the movement of ribosomes from RP transcripts to stress-induced mRNAs. Using tiling arrays, we show that osmotic stress yields a drop in the levels of RP pre-mRNAs in S. cerevisiae cell…
Nonsense-mediated decay mechanism is a possible modifying factor of clinical outcome in nonsense cd39 beta thalassemia genotype
2012
Nonsense-mediated mRNA decay (NMD) is a surveillance system to prevent the synthesis of non-functional proteins. In β-thalassemia, NMD may have a role in clinical outcome. An example of premature translation stop codons appearing for the first time is the β-globin cd39 mutation; when homozygous, this results in a severe phenotype. The aim of this study was to determine whether the homozygous nonsense cd39 may have a milder phenotype in comparison with IVS1,nt110/cd39 genotype. Genotypes have been identified from a cohort of 568 patients affected by β-thalassemia. These genotypes were compared with those found in 577 affected fetuses detected among 2292 prenatal diagnoses. The…
Nonsense polarity, RNA processing and decay in phage f1.
2011
Nonsense polarity in most cases depends on activation of cryptic transcription terminators. We found that the strong polar effect observed in the nonsense polar mutant R4 of phage f1, mapping in the 5’ proximal region of gene III, instead depends on enhanced instability of mutant mRNAs, whose pattern can be restored by reduction of RNase E activity. rne -(ts) E. coli strains allowed to explore the mechanisms underlying f1 mRNA processing and degradation. The major gene III species, a 1.8 Kb long molecule, appeared to be a secondary transcript, whose decay is modulated by a REP, located at its 3' end. The RNA pool of a mutagenized phage unable to form that structure, lacks completely that tr…