Inhibition of 5`- Cap Trimethylation Prevents Exosome Targeting of Telomerase RNA, Despite Promoting Increased 3`- end Oligoadenylation

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.