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The dharma of nonsense-mediated mRNA decay in mammalian cells
Maximilian Wei-Lin Popp1, Lynne E Maquat
1Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, Rochester, New York 14642, USA ; Center for RNA Biology, University of Rochester, Rochester, New York 14642, USA.
Abstract:
Mammalian-cell messenger RNAs (mRNAs) are generated in the nucleus from precursor RNAs (pre-mRNAs, which often contain one or more introns) that are complexed with an array of incompletely inventoried proteins. During their biogenesis, pre-mRNAs and their derivative mRNAs are subject to extensive cis-modifications. These modifications promote the binding of distinct polypeptides that mediate a diverse array of functions needed for mRNA metabolism, including nuclear export, inspection by the nonsense-mediated mRNA decay (NMD) quality-control machinery, and synthesis of the encoded protein product. Ribonucleoprotein complex (RNP) remodeling through the loss and gain of protein constituents before and after pre-mRNA splicing, during mRNA export, and within the cytoplasm facilitates NMD, ensuring integrity of the transcriptome. Here we review the mRNP rearrangements that culminate in detection and elimination of faulty transcripts by mammalian-cell NMD.
Insights
Mammalian messenger RNAs (mRNAs) undergo protein remodeling during biogenesis. This process is crucial for the nonsense-mediated mRNA decay (NMD) pathway to detect and eliminate faulty transcripts, ensuring transcriptome integrity.
Area of Science:
- Molecular Biology
- RNA Biology
- Cellular Processes
Background:
- Messenger RNAs (mRNAs) in mammalian cells are transcribed from precursor RNAs (pre-mRNAs) containing introns.
- These pre-mRNAs associate with numerous proteins, forming ribonucleoprotein complexes (RNPs).
- Extensive cis-modifications occur during mRNA biogenesis, influencing protein binding and function.
Purpose of the Study:
- To review the dynamic protein rearrangements (remodeling) of messenger ribonucleoprotein complexes (mRNPs).
- To explain how these rearrangements facilitate the detection and elimination of aberrant transcripts by the nonsense-mediated mRNA decay (NMD) pathway.
- To highlight the importance of mRNP remodeling in maintaining transcriptome integrity in mammalian cells.
Main Methods:
- Review of existing literature on mRNA biogenesis and processing.
- Analysis of protein-RNA interactions and their dynamic changes.
- Focus on the role of ribonucleoprotein complex remodeling in mRNA quality control.
Main Results:
- mRNA biogenesis involves sequential loss and gain of proteins associated with the RNA molecule.
- These dynamic mRNP rearrangements are critical for the proper functioning of the nonsense-mediated mRNA decay (NMD) pathway.
- NMD machinery relies on these remodeling events to distinguish between functional and faulty transcripts.
Conclusions:
- The dynamic remodeling of mRNPs is a fundamental aspect of mRNA metabolism in mammalian cells.
- This remodeling is essential for the efficacy of the NMD pathway in safeguarding the transcriptome.
- Understanding mRNP rearrangements provides insights into RNA quality control mechanisms.
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