title: The 5' guanosine tracts of human telomerase RNA are recognized by the G-quadruplex binding domain of the RNA helicase DHX36 and function to increase RNA accumulation.
abstract: Telomerase promotes telomere maintenance by copying a template within its integral RNA subunit to elongate chromosome ends with new telomeric repeats. Motifs have been defined within the telomerase RNA that contribute to mature RNA accumulation, holoenzyme catalytic activity, or enzyme recruitment to telomeres. Here, we describe a motif of human telomerase RNA (hTR), not previously characterized in a cellular context, comprised of several guanosine tracts near the RNA 5' end. These guanosine tracts together are recognized by the DEXH box RNA helicase DHX36. The helicase domain of DHX36 does not mediate hTR binding; instead, hTR interacts with the N-terminal accessory domain of DHX36 known to bind specifically to the parallel-strand G-quadruplex substrates resolved by the helicase domain. The steady-state level of DHX36-hTR interaction is low, but hTR guanosine tract substitutions substantially reduce mature hTR accumulation and thereby reduce telomere maintenance. These findings suggest that G-quadruplex formation in the hTR precursor improves the escape of immature RNP from degradation, but subsequently the G-quadruplex may be resolved in favor of a longer terminal stem. We conclude that G-quadruplex formation within hTR can stimulate telomerase-mediated telomere maintenance.
authors.affiliation: Molecular and Cell Biology, University of California, Berkeley, CA 94720-3200, USA.
authors.forename: Alec N
authors.initials: AN
authors.lastname: Sexton
authors.forename: Kathleen
authors.initials: K
authors.lastname: Collins
mesh_terms: D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D053487:DEAD-box RNA Helicases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006151:Guanosine / Q000737:chemistry; D057809:HEK293 Cells; D006801:Humans; D066298:In Vitro Techniques; D046912:Multiprotein Complexes; D009690:Nucleic Acid Conformation; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D012261:Ribonucleoproteins / Q000378:metabolism; D019098:Telomerase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000235:genetics / Q000378:metabolism
chemical_list: D046912:Multiprotein Complexes; D011994:Recombinant Proteins; D012261:Ribonucleoproteins; C422952:telomerase RNA; D006151:Guanosine; D012313:RNA; C509186:TERT protein, human; D019098:Telomerase; C466988:DHX36 protein, human; D053487:DEAD-box RNA Helicases