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 t stem cells derived from DC patients with a TERC mutation in the CR4-CR5 domain showed impaired myel

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

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

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

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

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

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

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

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

17 essential components of telomerase, TERT and TERC.

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

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

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

21 eported positive feedback regulation between TERC and the PI3K-AKT pathway that controlled cell proli

22 iogenesis and accumulation of snoRNAs beyond TERC, broadening our understanding of ncRNA dysregulatio

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

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

25 d the deficiency of AKT activation caused by TERC depletion.

26 minantly expressed in cancer and stem cells, TERC is ubiquitously expressed in normal somatic cells w

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

28 , downregulates the telomerase RNA component TERC, confers genomic stability and promotes DNA repair,

29 on-coding (nc) RNA telomerase RNA component (TERC) and RNAs involved in the maturation of TERC in PBM

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

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

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

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

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

35 c stabilization of telomerase RNA component (TERC), a therapeutically relevant long non-coding RNA (l

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

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

38 s and destabilizes telomerase RNA component (TERC).

39 maturation of the telomerase RNA component (TERC).

40 ommonly gained (including regions containing TERC and MYC) and lost regions (including regions contai

41 bsequent accumulation in mNG-NRAS-containing TERCs.

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

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

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

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

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

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

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

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

50 Compared with therapeutic mRNAs, engineered TERC RNA (eTERC) depends on avoiding nucleoside base mod

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

67 tant hESCs led to functional improvements in TERC levels and telomerase activity, with concomitant te

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

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

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

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

72 nita (DC) in patients harboring mutations in TERC, PARN, NOP10, NHP2, NAF1, or DKC1.

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

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

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

76 By associating with AU-rich sequences in TERC, HuB and HuD repressed the assembly of the TERT-TER

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

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

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

80 pathway and that RAS activation persists in TERCs, whereas endosomal EGFR does not significantly con

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

82 ions in telomere maintaining genes including TERC and TERT.

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

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

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

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

87 Intriguingly, TERC-induced activation of the PI3K-AKT pathway also pla

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

89 NOP10 mutations had short telomeres and low TERC levels.

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

91 ent, enriched in recycling endosome markers (TERC).

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

111 ation of TERC in PBMC, and the expression of TERC and 5'-3' Exoribonuclease 1 (XRN1) in extracellular

112 We found decreased expression of TERC in PBMC early in pregnant women who subsequently de

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

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

115 ant increase in mature, functional, forms of TERC, indicating that regulation of PAPD5 is a potential

116 y, our findings identify a novel function of TERC that regulates the PI3K-AKT pathway via positive fe

117 However, the functions of TERC in these telomerase-negative cells remain elusive.

118 ta (DC) by decreasing steady-state levels of TERC, the non-coding RNA component of telomerase.

119 Reduced levels of TERC, the telomerase RNA component, cause dyskeratosis c

120 h PARN is disrupted show decreased levels of TERC.

121 Mutations that cause reduced levels of TERC/hTR, the telomerase RNA component, are found in mos

122 TERC) and RNAs involved in the maturation of TERC in PBMC, and the expression of TERC and 5'-3' Exori

123 XRN1 involved in the maturation of TERC was also reduced in pregnancy and 5-year follow-up.

124 quired for posttranscriptional maturation of TERC.

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

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

127 ulation of posttranscriptional processing of TERC could improve hematopoietic output in DC.

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

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

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

131 88; 90%) and harbored either a TERT (45%) or TERC germ line mutation (32%).

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

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

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

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

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

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

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

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

140 significant telomere shortening and reduced TERC levels.

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

142 or, the dihydroquinolizinone RG7834, rescued TERC 3' end maturation and telomere length.

143 RNA degradation complex, partially restores TERC levels in immortalized DKC1 mutant cells, but it re

144 criptase activity and the long noncoding RNA TERC.

145 ssociating with the telomerase noncoding RNA TERC.

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

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

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

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

150 rse transcriptase (TERT) and telomerase RNA (TERC).

151 1 patients with short telomeres did not show TERC mutations.

152 Similarly, TERC regulated myeloid gene expression and Pol II promot

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

154 verse transcriptase TERT and the RNA subunit TERC.

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

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

157 reverse transcriptase hTERT and RNA template TERC/hTR.

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

159 xity involving telomere biology genes (TERT, TERC) and others like SFTPC and MUC5B.

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

161 B and HuD repressed the assembly of the TERT-TERC core complex.

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

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

164 Mechanistically, we revealed that TERC activated the transcription of target genes from th

165 Our findings show that TERC acts as a transcription factor, revealing a target

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

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

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

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

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

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

172 HuB and HuD competed with HuR for binding to TERC and antagonized the function of HuR that was previo

173 regulated by the PI3K-AKT pathway, bound to TERC promoter and suppressed its expression.

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

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

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

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