PNRC2 preferentially interacts with SMG5, impacting mRNA degradation processes.
Hyperphosphorylated Upf1 plays a crucial role in the recognition of substrates.
Downregulation of PNRC2 disrupts the interaction between SMG5 and Dcp1a.
Upf1, SMG5, and PNRC2 function at the same step in the NMD process.
SMG6 is required for efficient mRNA degradation involving Upf1.
There is a significant overlap between SMG5-dependent and PNRC2-dependent NMD substrates, suggesting a functional dominance of the SMG5-PNRC2 complex.
Simplified
In mammals, (NMD) functions in post-transcriptional gene regulation as well as mRNA surveillance. A key NMD factor, Upf1, becomes hyperphosphorylated by SMG1 kinase during the recognition of NMD substrates. Hyperphosphorylated Upf1 interacts with several factors including SMG5, SMG6, SMG7 and PNRC2 to trigger rapid mRNA degradation. However, the possible cross-talk among these factors and their selective use during NMD remain unknown. Here, we show that PNRC2 is preferentially complexed with SMG5, but not with SMG6 or SMG7, and that downregulation of PNRC2 abolishes the interaction between SMG5 and Dcp1a, a component of the decapping complex. In addition, tethering experiments reveal the function of Upf1, SMG5 and PNRC2 at the same step of NMD and the requirement of SMG6 for Upf1 for efficient mRNA degradation. Intriguingly, microarray results reveal the significant overlap of SMG5-dependent NMD substrates more with PNRC2-dependent NMD substrates than with SMG7-dependent NMD substrates, suggesting the functional dominance of SMG5-PNRC2, rather than SMG5-SMG7, under normal conditions. The results provide evidence that, to some extent, endogenous NMD substrates have their own binding preference for Upf1-interacting adaptors or effectors.
Key numbers
2.3×
Decrease in mRNA degradation by Upf1 downregulation
Observed in tethering experiments with SMG5, SMG6, and PNRC2.
2.5×
Decrease in mRNA degradation by PNRC2 downregulation
Measured during tethering assays with SMG5 and Upf1.
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Overlap of transcripts upregulated by SMG5 and PNRC2
Identified in microarray analyses of transcript regulation.
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