DIS3L2

DIS3L2

DIS3L2 is a gene that encodes a protein involved in RNA metabolism, specifically in the degradation of certain types of RNA molecules. This protein is part of the exosome complex, which is crucial for maintaining RNA homeostasis within the cell. Mutations in the DIS3L2 gene have been associated with Perlman syndrome, a rare congenital overgrowth disorder.

Structure

The DIS3L2 protein is a member of the RNase II family of exoribonucleases. It contains several domains that are important for its function, including an N-terminal PIN domain, which is involved in RNA binding, and a C-terminal RNB domain, which is responsible for its ribonuclease activity. The structure of DIS3L2 allows it to selectively degrade specific RNA substrates, distinguishing it from other exoribonucleases in the exosome complex.

Function

DIS3L2 plays a critical role in the degradation of uridylated RNA substrates. It is particularly important in the processing and turnover of non-coding RNAs, such as microRNAs and small interfering RNAs. By degrading these RNA molecules, DIS3L2 helps regulate gene expression and maintain cellular homeostasis.

RNA Degradation

The primary function of DIS3L2 is to degrade RNA molecules that have been marked for destruction by the addition of uridine residues at their 3' ends. This uridylation process is a signal for degradation, and DIS3L2 recognizes and binds to these uridylated RNAs, catalyzing their degradation into smaller fragments.

Clinical Significance

Mutations in the DIS3L2 gene have been linked to Perlman syndrome, a rare genetic disorder characterized by overgrowth, developmental delay, and an increased risk of Wilms' tumor. Perlman syndrome is an autosomal recessive condition, meaning that affected individuals inherit two copies of the mutated gene, one from each parent.

Perlman Syndrome

Perlman syndrome is associated with a variety of symptoms, including nephroblastomatosis, visceromegaly, and distinctive facial features. The role of DIS3L2 in RNA metabolism suggests that disruptions in RNA processing and degradation may contribute to the pathogenesis of this disorder.

Research Directions

Ongoing research is focused on understanding the precise mechanisms by which DIS3L2 recognizes and degrades its RNA substrates. Additionally, studies are investigating the broader implications of DIS3L2 dysfunction in other diseases and its potential as a therapeutic target.

See Also

• Exosome complex
• RNA metabolism
• Perlman syndrome

External Links

• "DIS3L2 Gene - NCBI"