regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay

Definition

Target type: biologicalprocess

Any process that modulates the frequency, rate or extent of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay. [GOC:obol]

Nonsense-mediated decay (NMD) is a critical surveillance pathway that eliminates aberrant mRNAs containing premature termination codons (PTCs) from the cytoplasm, preventing the production of truncated and potentially harmful proteins. This process plays a crucial role in maintaining the integrity of the proteome and ensuring proper cellular function. NMD is initiated during the translation of an mRNA molecule, specifically during the ribosome's journey along the transcript. If the ribosome encounters a PTC located upstream of a defined distance from the last exon-exon junction (typically 50-55 nucleotides), it triggers a cascade of events leading to the degradation of the mRNA. The core components of the NMD machinery include the UPF1, UPF2, and UPF3 proteins. UPF1, a key player in the NMD pathway, acts as a sensor for PTCs. When the ribosome encounters a PTC, UPF1 is recruited to the ribosome and interacts with the exon junction complex (EJC), which is deposited at exon-exon junctions during splicing. This interaction activates UPF1, marking the mRNA for degradation. UPF2 and UPF3 then join the complex, forming a trimeric complex that interacts with the decapping complex and the exosome. The decapping complex removes the 5' cap from the mRNA, rendering it vulnerable to degradation by the exosome, a multi-protein complex that degrades mRNAs from the 3' end. In addition to the core components, NMD involves various other factors, including SMG1, SMG5-7, and SMG9. SMG1 is a kinase that phosphorylates UPF1, facilitating its activation and interaction with other NMD factors. SMG5-7 and SMG9 play roles in the recruitment and stabilization of the decapping complex. NMD is a highly regulated process, and its efficiency is influenced by various factors, including the location of the PTC relative to the last exon-exon junction, the strength of the PTC, and the presence of specific mRNA sequences. NMD is essential for maintaining cellular homeostasis and protecting against the production of potentially harmful proteins. Mutations in NMD factors can lead to various genetic disorders characterized by the accumulation of truncated proteins and the disruption of cellular processes.'
"

Proteins (1)

Compounds (1)