title: Human Telomerase RNA Processing and Quality Control.
abstract: The non-coding RNA subunit of telomerase provides the template for telomerase activity. In diverse fungi, 3' end processing of telomerase RNA involves a single cleavage by the spliceosome. Here, we examine how human telomerase RNA (hTR) primary transcripts are processed into the mature form of precisely 451 nt. We find that the splicing inhibitor isoginkgetin mimics the effects of RNA exosome inhibition and causes accumulation of long hTR transcripts. Depletion of exosome components and accessory factors reveals functions for the cap binding complex (CBC) and the nuclear exosome targeting (NEXT) complex in hTR turnover. Whereas longer transcripts are predominantly degraded, shorter precursor RNAs are oligo-adenylated by TRF4-2 and either processed by poly(A)-specific ribonuclease (PARN) or degraded by the exosome. Our results reveal that hTR biogenesis involves a kinetic competition between RNA processing and degradation and suggest treatment options for telomerase insufficiency disorders.
authors.affiliation: Howard Hughes Medical Institute, Kansas City, MO 64110, USA; Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: Chi-Kang
authors.initials: CK
authors.lastname: Tseng
authors.affiliation: Howard Hughes Medical Institute, Kansas City, MO 64110, USA; Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Wang
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: Allison M
authors.initials: AM
authors.lastname: Burns
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: Morgan R
authors.initials: MR
authors.lastname: Schroeder
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: Martina
authors.initials: M
authors.lastname: Gaspari
authors.affiliation: Howard Hughes Medical Institute, Kansas City, MO 64110, USA; Stowers Institute for Medical Research, Kansas City, MO 64110, USA; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA. Electronic address: peb@stowers.org.
authors.forename: Peter
authors.initials: P
authors.lastname: Baumann
mesh_terms: D015152:Blotting, Northern; D006367:HeLa Cells; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D016133:Polymerase Chain Reaction; D012313:RNA / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional / Q000502:physiology*; D017381:Spliceosomes / Q000235:genetics; D019098:Telomerase / Q000378:metabolism*
chemical_list: C422952:telomerase RNA; D012313:RNA; D019098:Telomerase