{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMutations in the dyskerin protein, particularly within its N-terminal extension (NTE) domain, not only reduce TERC levels but also disrupt the normal processing of scaRNA13. In stem cells from dyskeratosis congenita patients harboring the del37L mutation, scaRNA13 transcripts exhibit abnormal 3′ extensions, indicating that proper 3′ end definition is compromised by these mutations. This finding underscores an essential role for dyskerin in ensuring accurate maturation of scaRNA13, a member of the small Cajal body-specific RNAs critical for RNA modification processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n\nIn addition, the study demonstrates that impairments in the scaRNA13 biogenesis associated with dyskerin NTE mutations can be counteracted. Both genome-editing repair of the del37L mutation and inhibition of the polymerase PAPD5—whose activity opposes the exoribonuclease PARN—restore normal scaRNA13 processing. These results reveal that the proper interplay between dyskerin and the PARN/PAPD5 axis is indispensable for scaRNA13 maturation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n\nStructural insights further bolster these conclusions; the cryo-EM model of human telomerase shows that the dyskerin NTE domain makes direct contact with terminal residues of the associated RNA, emphasizing its role in defining the 3′ end of scaRNA13. This mechanistic connection not only broadens our understanding of non-coding RNA regulation in telomere-associated diseases but also highlights potential therapeutic avenues for disorders linked to dyskerin dysfunction."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Neha Nagpal, Albert K Tai, Jayakrishnan Nandakumar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Domain specific mutations in dyskerin disrupt 3' end processing of scaRNA13."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkac706"}], "href": "https://doi.org/10.1093/nar/gkac706"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36018809"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36018809"}]}]}]}