title: Vault poly(ADP-ribose) polymerase is associated with mammalian telomerase and is dispensable for telomerase function and vault structure in vivo.
abstract: Vault poly(ADP-ribose) polymerase (VPARP) was originally identified as a minor protein component of the vault ribonucleoprotein particle, which may be involved in molecular assembly or subcellular transport. In addition to the association of VPARP with the cytoplasmic vault particle, subpopulations of VPARP localize to the nucleus and the mitotic spindle, indicating that VPARP may have other cellular functions. We found that VPARP was associated with telomerase activity and interacted with exogenously expressed telomerase-associated protein 1 (TEP1) in human cells. To study the possible role of VPARP in telomerase and vault complexes in vivo, mVparp-deficient mice were generated. Mice deficient in mVparp were viable and fertile for up to five generations, with no apparent changes in telomerase activity or telomere length. Vaults purified from mVparp-deficient mouse liver appeared intact, and no defect in association with other vault components was observed. Mice deficient in mTep1, whose disruption alone does not affect telomere function but does affect the stability of vault RNA, showed no additional telomerase or telomere-related phenotypes when the mTep1 deficiency was combined with an mVparp deficiency. These data suggest that murine mTep1 and mVparp, alone or in combination, are dispensable for normal development, telomerase catalysis, telomere length maintenance, and vault structure in vivo.
authors.affiliation: Ontario Cancer Institute/Advanced Medical Discovery Institute, Toronto, Ontario M5G 2C1, Canada. liuy3@ornl.gov
authors.forename: Yie
authors.initials: Y
authors.lastname: Liu
authors.forename: Bryan E
authors.initials: BE
authors.lastname: Snow
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Kickhoefer
authors.forename: Natalie
authors.initials: N
authors.lastname: Erdmann
authors.forename: Wen
authors.initials: W
authors.lastname: Zhou
authors.forename: Andrew
authors.initials: A
authors.lastname: Wakeham
authors.forename: Marla
authors.initials: M
authors.lastname: Gomez
authors.forename: Leonard H
authors.initials: LH
authors.lastname: Rome
authors.forename: Lea
authors.initials: L
authors.lastname: Harrington
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002999:Clone Cells; D018390:Gene Targeting; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011065:Poly(ADP-ribose) Polymerases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins; D019098:Telomerase / Q000378:metabolism*; D020394:Vault Ribonucleoprotein Particles / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D016601:RNA-Binding Proteins; C498415:Tep1 protein, mouse; D020394:Vault Ribonucleoprotein Particles; D011065:Poly(ADP-ribose) Polymerases; C449359:vault poly(ADP-ribose) polymerase; D019098:Telomerase