PNRC2 is a relatively small coactivator with a molecular weight of approximately 16 kDa . It is characterized by a proline-rich sequence, which is essential for its interaction with nuclear receptors. The protein contains an SH3 domain-binding motif (SEPPSPS) and an NR box-like sequence (LKTLL), which are critical for its function .
PNRC2 interacts with nuclear receptors in both ligand-dependent and ligand-independent manners. It has been shown to interact with orphan receptors such as steroidogenic factor 1 (SF1) and estrogen receptor-related receptor α1, as well as with the ligand-binding domains of various other nuclear receptors, including estrogen receptor, glucocorticoid receptor, progesterone receptor, thyroid receptor, retinoic acid receptor, and retinoid X receptor .
One of the significant functions of PNRC2 is its involvement in nonsense-mediated mRNA decay (NMD). NMD is a surveillance pathway that degrades mRNAs containing premature stop codons, preventing the production of truncated and potentially harmful proteins. PNRC2 acts as a bridge between the mRNA decapping complex and the NMD machinery, facilitating the degradation of aberrant mRNAs . It is required for the localization of UPF1/RENT1 to the P-body, a cellular structure involved in mRNA decay .
PNRC2 also plays a role in glucocorticoid receptor-mediated mRNA degradation. It interacts with the glucocorticoid receptor (NR3C1) in a ligand-dependent manner when the receptor is bound to the 5’ untranslated region (UTR) of target mRNAs. This interaction recruits the RNA helicase UPF1 and the mRNA-decapping enzyme DCP1A, leading to RNA decay .
Mutations or dysregulation of the PNRC2 gene have been associated with various diseases. For instance, PNRC2 is linked to Leydig Cell Hypoplasia, Type I, and Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2W . Additionally, PNRC2 is involved in pathways related to viral mRNA translation and the processing of capped intron-containing pre-mRNA .
Research on PNRC2 continues to uncover its diverse roles in cellular processes and its potential implications in disease. The recombinant form of PNRC2 is used in various experimental setups to study its function and interactions with other proteins. Understanding the mechanisms by which PNRC2 operates can provide insights into the regulation of gene expression and the maintenance of cellular homeostasis.