scholarly journals Mechanisms and Regulation of Nonsense-Mediated mRNA Decay and Nonsense-Associated Altered Splicing in Lymphoid Cells

2020 ◽  
Author(s):  
Jean-Marie Lambert ◽  
Mohamad Omar Ashi ◽  
Nivine Srour ◽  
Laurent Delpy ◽  
Jérôme Saulière
Keyword(s):  
Quality Control ◽  
Mrna Decay ◽  
Dominant Negative ◽  
Lymphoid Cells ◽  
Surveillance Systems ◽  
Rna Surveillance ◽  
Accelerated Degradation ◽  
Premature Termination Codons ◽  
Rna Quality Control ◽  
Nonsense Mediated Mrna Decay

The presence of premature termination codons (PTCs) in transcripts is dangerous for the cell as they encode potentially deleterious truncated proteins that can act with dominant-negative or gain-of-function effects. To avoid synthesis of these shortened polypeptides, several RNA surveillance systems can be activated to decrease the level of PTC-containing mRNAs. Nonsense-mediated mRNA decay (NMD) ensures an accelerated degradation of mRNAs harboring PTCs by using several key NMD factors such as up-frameshift (UPF) proteins. Another pathway called nonsense-associated altered splicing (NAS) upregulates transcripts that have skipped disturbing PTCs by alternative splicing. Therefore, these RNA quality control processes eliminate abnormal PTC-containing mRNAs from the cells by using positive and negative responses. In this review, we will describe the general mechanisms of NMD and NAS and their respective involvement in the decay of aberrant immunoglobulin and TCR transcripts in lymphoid cells.

scholarly journals Mechanisms and Regulation of Nonsense-Mediated mRNA Decay and Nonsense-Associated Altered Splicing in Lymphocytes

2020 ◽  
Vol 21 (4) ◽  
pp. 1335 ◽  
Author(s):  
Jean-Marie Lambert ◽  
Mohamad Omar Ashi ◽  
Nivine Srour ◽  
Laurent Delpy ◽  
Jérôme Saulière
Keyword(s):  
Quality Control ◽  
Alternative Splicing ◽  
Mrna Decay ◽  
Dominant Negative ◽  
Surveillance Systems ◽  
Rna Surveillance ◽  
Accelerated Degradation ◽  
Premature Termination Codons ◽  
Rna Quality Control ◽  
Nonsense Mediated Mrna Decay

The presence of premature termination codons (PTCs) in transcripts is dangerous for the cell as they encode potentially deleterious truncated proteins that can act with dominant-negative or gain-of-function effects. To avoid the synthesis of these shortened polypeptides, several RNA surveillance systems can be activated to decrease the level of PTC-containing mRNAs. Nonsense-mediated mRNA decay (NMD) ensures an accelerated degradation of mRNAs harboring PTCs by using several key NMD factors such as up-frameshift (UPF) proteins. Another pathway called nonsense-associated altered splicing (NAS) upregulates transcripts that have skipped disturbing PTCs by alternative splicing. Thus, these RNA quality control processes eliminate abnormal PTC-containing mRNAs from the cells by using positive and negative responses. In this review, we describe the general mechanisms of NMD and NAS and their respective involvement in the decay of aberrant immunoglobulin and TCR transcripts in lymphocytes.

scholarly journals The RNA quality control pathway nonsense-mediated mRNA decay targets cellular and viral RNAs to restrict KSHV

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Yang Zhao ◽  
Xiang Ye ◽  
Myriam Shehata ◽  
William Dunker ◽  
Zhihang Xie ◽  
...  
Keyword(s):  
Quality Control ◽  
Mrna Decay ◽  
Viral Rnas ◽  
Rna Quality ◽  
Rna Quality Control ◽  
Nonsense Mediated Mrna Decay

scholarly journals From Yeast to Mammals, the Nonsense-Mediated mRNA Decay as a Master Regulator of Long Non-Coding RNAs Functional Trajectory

2021 ◽  
Vol 7 (3) ◽  
pp. 44
Author(s):  
Sara Andjus ◽  
Antonin Morillon ◽  
Maxime Wery
Keyword(s):  
Quality Control ◽  
Mrna Decay ◽  
Environmental Changes ◽  
Master Regulator ◽  
Rna Surveillance ◽  
Multiple Functions ◽  
Functional Roles ◽  
Nonsense Mediated Mrna Decay ◽  
Non Coding Rnas ◽  
Molecular Bases

The Nonsense-Mediated mRNA Decay (NMD) has been classically viewed as a translation-dependent RNA surveillance pathway degrading aberrant mRNAs containing premature stop codons. However, it is now clear that mRNA quality control represents only one face of the multiple functions of NMD. Indeed, NMD also regulates the physiological expression of normal mRNAs, and more surprisingly, of long non-coding (lnc)RNAs. Here, we review the different mechanisms of NMD activation in yeast and mammals, and we discuss the molecular bases of the NMD sensitivity of lncRNAs, considering the functional roles of NMD and of translation in the metabolism of these transcripts. In this regard, we describe several examples of functional micropeptides produced from lncRNAs. We propose that translation and NMD provide potent means to regulate the expression of lncRNAs, which might be critical for the cell to respond to environmental changes.

scholarly journals Regulation of Multiple Core Spliceosomal Proteins by Alternative Splicing-Coupled Nonsense-Mediated mRNA Decay

2008 ◽  
Vol 28 (13) ◽  
pp. 4320-4330 ◽  
Author(s):  
Arneet L. Saltzman ◽  
Yoon Ki Kim ◽  
Qun Pan ◽  
Matthew M. Fagnani ◽  
Lynne E. Maquat ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Mrna Decay ◽  
Splice Variants ◽  
Cellular Functions ◽  
Regulate Gene Expression ◽  
Premature Termination Codons ◽  
Microarray Profiling ◽  
Nonsense Mediated Mrna Decay ◽  
Regulate Gene

ABSTRACT Alternative splicing (AS) can regulate gene expression by introducing premature termination codons (PTCs) into spliced mRNA that subsequently elicit transcript degradation by the nonsense-mediated mRNA decay (NMD) pathway. However, the range of cellular functions controlled by this process and the factors required are poorly understood. By quantitative AS microarray profiling, we find that there are significant overlaps among the sets of PTC-introducing AS events affected by individual knockdown of the three core human NMD factors, Up-Frameshift 1 (UPF1), UPF2, and UPF3X/B. However, the levels of some PTC-containing splice variants are less or not detectably affected by the knockdown of UPF2 and/or UPF3X, compared with the knockdown of UPF1. The intron sequences flanking the affected alternative exons are often highly conserved, suggesting important regulatory roles for these AS events. The corresponding genes represent diverse cellular functions, and surprisingly, many encode core spliceosomal proteins and assembly factors. We further show that conserved, PTC-introducing AS events are enriched in genes that encode core spliceosomal proteins. Where tested, altering the expression levels of these core spliceosomal components affects the regulation of PTC-containing splice variants from the corresponding genes. Together, our results show that AS-coupled NMD can have different UPF factor requirements and is likely to regulate many general components of the spliceosome. The results further implicate general spliceosomal components in AS regulation.

scholarly journals A UPF1 variant drives conditional remodeling of nonsense-mediated mRNA decay

2021 ◽  
Author(s):  
Sarah E. Fritz ◽  
Soumya Ranganathan ◽  
J. Robert Hogg
Keyword(s):  
Gene Expression ◽  
Mrna Decay ◽  
Gene Expression Regulation ◽  
Translation Termination ◽  
Translational Repression ◽  
The Core ◽  
Human Genes ◽  
Rna Quality Control ◽  
Nonsense Mediated Mrna Decay

AbstractThe nonsense-mediated mRNA decay (NMD) pathway monitors translation termination to degrade transcripts with premature stop codons and regulate thousands of human genes. Due to the major role of NMD in RNA quality control and gene expression regulation, it is important to understand how the pathway responds to changing cellular conditions. Here we show that an alternative mammalian-specific isoform of the core NMD factor UPF1, termed UPF1LL, enables condition-dependent remodeling of NMD specificity. UPF1LL associates more stably with potential NMD target mRNAs than the major UPF1SL isoform, expanding the scope of NMD to include many transcripts normally immune to the pathway. Unexpectedly, the enhanced persistence of UPF1LL on mRNAs supports induction of NMD in response to rare translation termination events. Thus, while canonical NMD is abolished by translational repression, UPF1LL activity is enhanced, providing a mechanism to rapidly rewire NMD specificity in response to cellular stress.

NMD-Based Gene Regulation—A Strategy for Fitness Enhancement in Plants?

2019 ◽  
Vol 60 (9) ◽  
pp. 1953-1960 ◽  
Author(s):  
Misato Ohtani ◽  
Andreas Wachter
Keyword(s):  
Quality Control ◽  
Gene Regulation ◽  
Current Knowledge ◽  
Qualitative And Quantitative ◽  
Rna Quality ◽  
Quantitative Level ◽  
Splicing Variants ◽  
Rna Quality Control ◽  
Nonsense Mediated Mrna Decay ◽  
Environmental Responses

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 responses. In this review, we will briefly summarize our current knowledge of the recognition and degradation of NMD targets, followed by an account of NMD’s regulation and physiological functions. We will specifically discuss plant-specific aspects of RNA quality control and its functional contribution to the fitness and environmental responses of plants.

Regulated and quality-control mRNA turnover pathways in eukaryotes

2010 ◽  
Vol 38 (6) ◽  
pp. 1506-1510 ◽  
Author(s):  
Boris Reznik ◽  
Jens Lykke-Andersen
Keyword(s):  
Quality Control ◽  
Rna Processing ◽  
Rna Localization ◽  
Rna Degradation ◽  
Eukaryotic Cells ◽  
Mrna Turnover ◽  
Surveillance Systems ◽  
Rna Turnover ◽  
Rna Surveillance ◽  
Multiple Levels

Gene expression can be regulated at multiple levels, including transcription, RNA processing, RNA localization, translation and, finally, RNA turnover. RNA degradation may occur at points along the processing pathway or during translation as it undergoes quality control by RNA surveillance systems. Alternatively, mRNAs may be subject to regulated degradation, often mediated by cis-encoded determinants in the mRNA sequence that, through the recruitment of trans factors, determine the fate of the mRNA. The aim of the present review is to highlight mechanisms of regulated and quality-control RNA degradation in eukaryotic cells, with an emphasis on mammals.

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