GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE293nnn/GSE293934/suppl/filelist.txtftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE293nnn/GSE293934/suppl/GSE293934_RAW.tarftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE293nnn/GSE293934/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE293934GEOGSEfalseInhibition of 5`- Cap Trimethylation Prevents Exosome Targeting of Telomerase RNA, Despite Promoting Increased 3`- end OligoadenylationMutations that impact maturation of human telomerase RNA (hTR) are common in telomere-biology disorders. Here, we describe sequential posttranscriptional modifications that coordinate hTR biogenesis and decay. Initially, TGS1-mediated 5`- cap trimethylation targets long genomically extended hTR precursors for degradation. Prevention of trimethylation results in accumulation of nucleolar 3`- end extended precursors, evading MTR4 recognition and degradation by the exosome, which in turn facilitates processing into mature hTR. In a second step, 3`- end oligoadenylation by PAPD5 promotes degradation of mature hTR, a process that remains dependent on 5`- cap modifications, as prevention of trimethylation inhibits decay of 3`- end oligoadenylated molecules. Combined inhibition of 5`- cap trimethylation and 3`- end oligoadenylation synergistically increases hTR in cells harboring pathogenic mutations in telomerase. These data reveal a precise interplay between 5`- and 3`- end posttranscriptional modifications that dictate hTR fate and highlight the potential of RNA therapeutics for treatment of telomere-biology disorders.2026/04/08GSE293934GSM8894780GSM8894781GSM8894782GSM8894783GSM8894784GSM8894785GSM8894786GSM8894787GSM8894788GSM889477915520293934Homo sapiens[41571462]