Disease mutations in two parts of dyskerin do not stop it from pairing but disrupt its binding to telomerase RNA

Dyskerin dimerization has been biochemically demonstrated for the first time.

• Dyskerin is essential for the production of H/ACA RNAs, including the human telomerase RNA.
• Mutations in the N-terminal extension and α2' helix of dyskerin are linked to X-linked dyskeratosis congenita, a disorder associated with premature aging.
• Some mutations disrupt dyskerin's interaction with human telomerase RNA, leading to reduced telomerase activity.
• Dimerization of dyskerin occurs independently of RNA and is not affected by disease-associated mutations in the N-terminal extension or α2' helix.
• Mutations in these regions specifically impair the binding of dyskerin to human telomerase RNA.

Simplified