ライフサイエンスコーパス: TERC

1 TERC expression level remained a significant prognostic

2 TERC reduction (a TBD-associated gene) in normal BMSCs b

3 TERC(-/-) mice at generation 2 and TERT(-/-) mice at gen

4 ) identified two loci on chromosomes 3q26.2 (TERC) and 10q24.33 (OBFC1) that are associated with the

5 One additional patient carried a TERC mutation.

6 e predictor for the presence or absence of a TERC or TERT gene mutation.

7 2-member extended family with AD DC due to a TERC gene deletion.

8 ding the telomerase catalytic component) and TERC/hTR (the telomerase RNA template) were measured usi

9 (RR) of relapse and levels of TERT mRNA and TERC expression.

10 For each doubling in TERT mRNA and TERC level, the RR increased by a factor of 1.16 (95% CI

11 utant and control iPSCs upregulated TERT and TERC expression compared with parental fibroblasts, but

12 were screened for variation in the TERT and TERC genes by direct sequencing; an additional 1,472 con

13 and 198 controls for variations in TERT and TERC genes.

14 The spectrum of mutations in TERT and TERC varies for these diseases and may in part explain t

15 roles that CIRP plays in regulating TERT and TERC, and reveal a new class of telomerase modulators in

16 essential components of telomerase, TERT and TERC.

17 ponents TERT, the reverse transcriptase, and TERC, the RNA template, cause autosomal dominant dyskera

18 F1R, INSR, PROP1, or TRX delay or that ATM + TERC, BubR1, klotho, LMNA, PRDX1, p53, WRN + TERC, or TO

19 Telomere length differed between TERC(-/-) and TERT(-/-) mice, whereas PH severity was si

20 Patients with mutations in both TERC alleles have not yet been reported.

21 hortest compared with other DC subtypes, but TERC levels were normal.

22 (-11)) and with the telomerase RNA component TERC (rs1317082, P = 1.1 x 10(-8)).

23 , we confirmed the telomerase RNA component (TERC) as a gene associated with LTL (P = 1.1 x 10(-5)).

24 The telomerase RNA component (TERC) is a critical determinant of cellular self-renewal

25 ical limitation in telomerase RNA component (TERC) levels to restore telomere maintenance and self-re

26 transcriptase (TERT) and the RNA component (TERC) of the telomerase complex.

27 tase (TERT) or the telomerase RNA component (TERC) telomerase genes.

28 iptase (TERT), the telomerase RNA component (TERC), and the TERC-binding protein dyskerin.

29 Telomerase RNA component (TERC), the RNA component and TERT the enzymatic componen

30 maturation of the telomerase RNA component (TERC).

31 Diminished TERC levels and the increased proportion of oligo(A) for

32 a patient with DKC who inherited 2 distinct TERC sequence variants from her parents; a deletion (216

33 which the known susceptibility genes (DKC1, TERC, and TERT) belong to the telomere maintenance pathw

34 latives, DC probands with mutations in DKC1, TERC, or TERT or 298 control subjects.

35 rt telomeres and germline mutations in DKC1, TERC, TERT, or NOP10, but approximately 60% of DC patien

36 osomal-dominant DC and no mutations in DKCI, TERC, or TERT.

37 ponents of the telomerase complex (dyskerin, TERC, TERT, and NOP10), important in the maintenance of

38 ponents of the telomerase complex (dyskerin, TERC, TERT, NOP10, and NHP2), and recently in one compon

39 noncoding RNA genes, including, for example, TERC, which encodes the telomerase RNA, exhibit extensiv

40 s were observed to have higher-than-expected TERC levels compared with controls.

41 ls from family members haploinsufficient for TERC have very short telomeres.

42 zed by restoring PARN, which is limiting for TERC maturation in cells.

43 gical material using BAC clones specific for TERC serves as an independent screening test for HSIL an

44 point mutations in the telomerase RNA gene (TERC) in each family.

45 RNA component of the human telomerase gene (TERC) on chromosome band 3q26, and repeat sequences spec

46 ting in a gain of the human telomerase gene (TERC).

47 s of the human telomerase RNA template gene (TERC) have been described in patients with acquired apla

48 Here, we generated TERC (telomerase RNA) gene knockouts in telomerase posit

49 Five of the loci contain candidate genes (TERC, TERT, NAF1, OBFC1 and RTEL1) that are known to be

50 Only 3 of 210 cases showed heterozygous TERC mutations: both nucleotide 305 (n305) (G>A) and n32

51 ird of patients whose tumors had the highest TERC expression level had an RR of 2.06 (95% CI, 1.14 to

52 y of the human telomerase RNA component (hTR/TERC).

53 competed for binding to telomerase RNA (hTR/TERC), thereby inhibiting endogenous telomerase activity

54 ng telomerase-positive cells and their human TERC knockout-derived ALT human cell lines, we show that

55 bition was also associated with increases in TERC stability, telomerase activity, and telomere elonga

56 A heterozygous mutation in TERC also was found in one family.

57 ons in DKC1, while heterozygous mutations in TERC (telomerase RNA component) and TERT (telomerase rev

58 atients with BMF had pathogenic mutations in TERC or TERT.

59 Mutations in TERC, the gene for the RNA component of telomerase, caus

60 failure syndrome, is caused by mutations in TERC, the RNA component of telomerase.

61 A similar reduction in TERC levels is also seen when the mutant NOP10 is expres

62 The limited amount of active telomerase in TERC RNA haploinsufficiency may not be able to maintain

63 Variants in TERC and TERT can impede telomere elongation causing ste

64 genic status of newly identified variants in TERC or TERT can be quite challenging.

65 P = 3.72 x 10(-14)) at a locus that includes TERC, which encodes the telomerase RNA component.

66 ions in telomere maintaining genes including TERC and TERT.

67 merase, and show that strategies to increase TERC expression may be therapeutically beneficial in DC

68 ciated domain-containing 5 (PAPD5) increased TERC levels in PARN-mutant patient cells.

69 ediated through KLF8 upregulation, increased TERC and TERT expression, or altered splicing of DVL2 tr

70 d gene) in normal BMSCs by small interfering TERC-RNA (siTERC-RNA) recapitulated the TBD-BMSC phenoty

71 Lead SNPs at two loci (TERC and TERT) associate with several cancers and other

72 NOP10 mutations had short telomeres and low TERC levels.

73 knockdown of NHP2 in human cells led to low TERC levels, but this reduction was not observed after G

74 n association with the RNA template molecule TERC, and controlling cell growth.

75 Individuals in our families with mutated TERC did not have physical signs of dyskeratosis congeni

76 cessing and increased destruction of nascent TERC RNA transcripts, resulting in telomerase deficiency

77 entification of risk alleles for glioma near TERC and TERT that also associate with telomere length i

78 rs6793295 a missense mutation in LRCC34 near TERC), 5q22.1 (rs73227498 between NREP and EPB41L4A), 10

79 A further CRC polymorphism near TERC also showed evidence of association with EC (OR = 0

80 p15, MUC5B at 11p15 and the 3q26 region near TERC, and we identified seven newly associated loci (Pme

81 Alleles associated with glioma risk near TERC and TERT were strongly associated with longer LTL (

82 associated with glioma risk, rs1920116 (near TERC), that reached genome-wide significance (Pcombined

83 children of affected parents who have normal TERC genes, parental telomeres are again similar in leng

84 novel mutations in the DKC1 gene and 3 novel TERC mutations responsible for the X-linked and autosoma

85 as a different impact on the accumulation of TERC compared with dyskerin, NOP10, and NHP2.

86 posttranscriptional 3' oligo-adenylation of TERC would counteract the deleterious effects of PARN mu

87 ored whether gain of 3q and amplification of TERC could predict progression from CIN1/CIN2 to CIN3 an

88 he detection of 3q gain and amplification of TERC in routinely collected Pap smears can assist in ide

89 telomerase complex through direct binding of TERC and regulates Cajal body localization of the telome

90 ate a new role for PARN in the biogenesis of TERC and provide a mechanism linking PARN mutations to t

91 In studying the immunologic consequences of TERC mutations, severe B lymphopenia and decreased immun

92 diagnostic tool for the direct detection of TERC gains in Pap smears.

93 While expression of TERC, the RNA component of telomerase, is widespread, th

94 he increased proportion of oligo(A) forms of TERC are normalized by restoring PARN, which is limiting

95 h PARN is disrupted show decreased levels of TERC.

96 quired for posttranscriptional maturation of TERC.

97 Here, we determined that overexpression of TERC increased telomere length in PARN-deficient cells a

98 Here we studied the prevalence of TERC and TERT gene mutations and of telomere shortening

99 While a reduction of TERC levels is not a universal feature of DC, it can be

100 ance of a mutation in the promoter region of TERC producing a telomeropathy.

101 Deep sequencing of TERC RNA 3' termini shows that PARN is required for remo

102 hich contains a template-bearing RNA (TER or TERC) and a protein reverse transcriptase.

103 carriers of all of the mutations in TERT or TERC had shorter telomeres than age-matched family membe

104 , which in some cases associate with TERT or TERC mutations.

105 Thus, mutations in TERT or TERC that result in telomere shortening over time confer

106 n and telomerase complex components (TERT or TERC) was established.

107 sociated mucocutaneous features, and others (TERC and TERT) for more subtle presentation as telomerop

108 In patients with BMF, pathogenic TERC or TERT gene mutations were invariably associated w

109 of TCAB1 by using RNA interference prevents TERC from associating with Cajal bodies, disrupts telome

110 significant telomere shortening and reduced TERC levels.

111 factor NF-Y, likely responsible for reduced TERC levels, decreased telomerase activity, and short te

112 Human telomerase RNA TERC occupies telomeres and Wnt pathway genes.

113 Mutations in the human telomerase RNA (TERC) occur in autosomal dominant dyskeratosis congenita

114 e reverse transcriptase, the telomerase RNA (TERC), and dyskerin.

115 n in the gene-encoding human telomerase RNA (TERC), resulting in telomere shortening.

116 1 patients with short telomeres did not show TERC mutations.

117 sociated with telomere biology, specifically TERC, DKC1, RTEL1, and TERF1.

118 verse transcriptase TERT and the RNA subunit TERC.

119 gether with the RNA component of telomerase (TERC), is required to maintain telomere integrity.

120 c disorders (GATA2, RUNX1), telomeropathies (TERC, TERT, RTEL1), ribosome disorders (SBDS, DNAJC21, R

121 rse transcriptase, TERT and an RNA template, TERC, and other components, including the pseudouridine

122 elomerase or telomere-binding protein (TERT, TERC, DKC1, NOP10, or TINF2).

123 We discovered that TERC upregulation is a feature of the pluripotent state,

124 Because of the possibility that TERC mutations might underlie seemingly acquired forms o

125 the telomerase RNA component (TERC), and the TERC-binding protein dyskerin.

126 l silencing accompanies a 3' deletion at the TERC locus.

127 qually short in all individuals carrying the TERC gene deletion irrespective of their age.

128 DKC, at least secondary to mutations in the TERC gene, is an improbable diagnosis in patients with o

129 e a mutation in the CCAAT box (GCAAT) of the TERC gene promoter in a family in which multiple members

130 mutation (37A>G) in the other allele of the TERC gene.

131 When TERC is limiting, this preference leads to the accelerat

132 d to its decreased ability to associate with TERC and telomerase activity.

133 In the new families described with TERC mutations, there is further evidence of disease ant

134 TERC, BubR1, klotho, LMNA, PRDX1, p53, WRN + TERC, or TOP3B accelerate mouse aging.