UPF3B

Overview

UPF3B (Up-frameshift protein 3B) is a protein encoded by the UPF3B gene in humans. It is a crucial component of the nonsense-mediated mRNA decay (NMD) pathway, which is a cellular mechanism that degrades mRNA transcripts containing premature stop codons, thereby preventing the production of truncated and potentially harmful proteins.

Structure

The UPF3B protein is part of the UPF family, which includes UPF1, UPF2, and UPF3A. UPF3B is characterized by its RNA-binding domains and its ability to interact with other NMD factors. The protein is predominantly located in the nucleus but shuttles to the cytoplasm where it performs its function in mRNA surveillance.

Function

UPF3B plays a pivotal role in the NMD pathway by acting as a bridge between the exon-junction complex (EJC) and other NMD factors such as UPF2 and UPF1. Upon recognition of a premature termination codon, UPF3B facilitates the recruitment of UPF1 to the mRNA, which is essential for the initiation of the decay process. This ensures that faulty mRNAs are rapidly degraded, maintaining the fidelity of gene expression.

Clinical Significance

Mutations in the UPF3B gene have been associated with various neurodevelopmental disorders, including intellectual disability, autism spectrum disorder, and schizophrenia. These mutations can lead to the production of dysfunctional UPF3B protein, impairing the NMD pathway and resulting in the accumulation of defective mRNAs and proteins.

Research and Studies

Recent studies have focused on understanding the specific mutations in UPF3B that contribute to disease phenotypes. Researchers are also exploring the broader implications of NMD pathway dysfunction in human health and disease, including its role in cancer and other genetic disorders.

Also see

• Nonsense-mediated mRNA decay
• UPF1
• UPF2
• Exon-junction complex
• Intellectual disability
• Autism spectrum disorder