Novel pathological variants of NHP2 affect N-terminal domain flexibility, protein stability, H/ACA Ribonucleoprotein (RNP) complex formation and telomerase activity.

ABSTRACT: Telomere biology disorders (TBDs) are characterized by short telomeres, premature aging, bone marrow failure and cancer predisposition. Germline mutations in NHP2, encoding for one component of the telomerase cofactor H/ACA RNA binding complex together with Dyskerin, NOP10 and GAR1, have been previously reported in rare cases of TBDs. Here, we report two novel NHP2 variants (NHP2-A39T and NHP2-T44M) identified in a compound heterozygous patient affected by premature aging, bone marrow failure/myelodysplastic syndrome and gastric cancer. Although still able to support cell viability, both variants reduce the levels of hTR, the telomerase RNA component, and telomerase activity, expanding the panel of NHP2 pathological variants. Furthermore, both variants fail to be incorporated in the H/ACA

SUBMITTER: Malinski B 

PROVIDER: S-EPMC10508036 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature