The Nonsense-mediated mRNA decay (NMD) pathway selectively degrades mRNAs harboring premature termination codons (PTCs) but also regulates the abundance of a large number of cellular RNAs. The central role of NMD in the control of gene expression requires the existence of buffering mechanisms that tightly regulate the magnitude of this pathway. Here, we will focus on the mechanism of NMD with an emphasis on the role of RNA helicases in the transition from NMD complexes that recognize a PTC to those that promote mRNA decay. We will also review recent strategies aimed at uncovering novel trans-acting factors and their functional role in the NMD pathway. Finally, we will describe recent progress in the study of the physiological role of the NMD response.
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http://dx.doi.org/10.1093/nar/gkw010 | DOI Listing |
bioRxiv
December 2024
Department of Molecular Genetics, Center for RNA Biology, The Ohio State University, Columbus, OH, 43210.
Pre-mRNA splicing, carried out in the nucleus by a large ribonucleoprotein machine known as the spliceosome, is functionally and physically coupled to the mRNA surveillance pathway in the cytoplasm called nonsense mediated mRNA decay (NMD). The NMD pathway monitors for premature translation termination signals, which can result from alternative splicing, by relying on the exon junction complex (EJC) deposited on exon-exon junctions by the spliceosome. Recently, multiple genetic screens in human cell lines have identified numerous spliceosome components as putative NMD factors.
View Article and Find Full Text PDFClin Genet
January 2025
Prenatal Diagnosis and Fetal Medicine Department, Human Genetics and Genome Research Institute, National Research Centre (NRC), Cairo, Egypt.
SUMOylation involves covalent attachment of small ubiquitin-like modifier (SUMO) proteins to specific lysine residues on target proteins and regulates various aspects of their function. Sentrin-specific proteases (SENPs) are key players in both the conjugation reaction of SUMO proteins to their targets and the subsequent deconjugation of SUMO-conjugated substrates. Here, we provide the first comprehensive prenatal description of a lethal syndrome linked to a novel homozygous stop-gain variant in SENP7 c.
View Article and Find Full Text PDFSci Rep
January 2025
Neuroscience Center, King Fahad Specialist Hospital, Dammam, Saudi Arabia.
Neuromuscular diseases (NMD) are a group of neurological diseases that manifest with various clinical symptoms affecting different components of the peripheral nervous system, which play a role in voluntary body movements control. The primary objective of this study is to explore the diagnostic efficacy of a combined genetic and biochemical testing approach for patients with neuromuscular diseases with diverse presentations in a population with high rate of consanguinity. Genetic testing was performed using selected Next Generation Sequencing (NGS) gene panels and whole exome sequencing on the peripheral blood sample from the patients.
View Article and Find Full Text PDFMol Biol (Mosk)
December 2024
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.
Eukaryotic translation release factor eRF1 is an important cellular protein that plays a key role in translation termination, nonsense-mediated mRNA decay (NMD), and readthrough of stop codons. The amount of eRF1 in the cell influences all these processes. The mechanism of regulation of eRF1 translation through an autoregulatory NMD-dependent expression circuit has been described for plants and fungi, but the mechanisms of regulation of human eRF1 translation have not yet been studied.
View Article and Find Full Text PDFFASEB J
December 2024
State Key Laboratory of Microbial Technology, Shandong University-Qingdao Campus, Qingdao, P.R. China.
Mammalian spermatogenesis is a tightly controlled cellular process including spermatogonial development and differentiation, meiosis of spermatocyte, and the morphological specification of haploid spermatozoa, during which the post-transcriptional gene regulations are vital but poorly understood. Nonsense-mediated mRNA decay (NMD), a highly conserved post-transcriptional regulatory mechanism of gene expression in eukaryotes, recently emerges as a licensing mechanism in cell fate transition, including stem cell differentiation and organogenesis. The function of NMD in spermatogonial development remains elusive.
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