GUARDIN

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GUARDIN, a p53-inducible effector, is critical for guarding the de novo structure of DNA and genomic integrity.

Annotated Information

Approved Symbol

GUARDIN

Approved Name

GUARDIN, long non coding transcriptional activator of miR34a (HGNC:52548)

Alias

LINC01759, long intergenic non-protein coding RNA 1759, LNCTAM34A (HGNC:52548)

Characteristics

GUARDIN is located between the genes encoding miR-34a and hexose-6-phosphate dehydrogenase/glucose 1-dehydrogenase (H6PD).[1] This region is part of the FRA1A(aphidicolin type, common, Fra(1)(P36)) fragile site that is frequently lost in human cancers.[2] GUARDIN silencing triggered apoptosis and senescence, enhanced cytotoxicity of additional genotoxic stress and inhibited cancer xenograft growth. GUARDIN may constitute a target for cancer treatment.[3]

Function

a, Expression of the lncRNA GUARDIN is induced upon DNA damage by direct p53 transcriptional activation in order to control genome stability by multiple mechanisms. b, Thanks to several miR-23a binding sites, GUARDIN is able to sequester this miRNA and to subsequently increase expression of TRF2, an essential factor devoted to capping and protection of telomere termini. c, GUARDIN also acts as a molecular scaffold to promote the interaction between BRCA1 and its partner BARD1, thus favouring the formation of this protein complex fundamental in DNA repair. The combinatorial effect of these different GUARDIN functions leads to cell survival, antagonizing the pro-apoptotic pathway promoted by p53 following DDR.[3]

GUARDIN has a role in regulation of cell viability as it is necessary for preventing chromosome end-to-end fusion through maintaining the expression of telomeric repeat-binding factor 2 (TRF2) by sequestering microRNA-23a.[3] GUARDIN modulates the cytotoxic effect of p53. [1] GUARDIN interacts with BRCA1 and BARD1 and is essential for the stabilization of BRCA1. [1] GUARDIN protects genomic integrity through TRF2 and BRCA1. [1]

Regulation

GUARDIN expression is primarily regulated by wild-type p53, and is strongly induced following DNA damage [1].

Expression

GUARDIN expression is primarily regulated by wild-type p53. However, it was detectable in TP53-null cells and in tumours with mutations in TP53, albeit at low levels.GUARDIN transcripts were concurrently reduced in a proportion of colon cancers with gene copy number loss.[1]

Disease

  • Colon cancer [1]

Labs working on this lncRNA

  • Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Disease, CAS Centre for Excellence in Cell and Molecular Biology, Innovation Centre for Cell Signalling Network, School of Life Sciences, University of Science and Technology of China, Hefei, China
  • Translational Research Institute, Henan Provincial People’s Hospital, Zhengzhou, China
  • Department of Gene Therapy and Regulation of Gene Expression, Center for Applied Medical Research, University of Navarra, Pamplona, Spain

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Hu WL, Jin L, Xu A, Wang YF, Thorne RF, Zhang XD et al. GUARDIN is a p53-responsive long non-coding RNA that is essential for genomic stability[J]. Nature cell biology. 2018, 20(4):492-502.
  2. Georgakilas AG, Tsantoulis P, Kotsinas A, Michalopoulos I, Townsend P & Gorgoulis VG. Are common fragile sites merely structural domains or highly organized “functional” units susceptible to oncogenic stress?[J]. Cellular and molecular life sciences. 2014, 71(23):4519-4544.
  3. 3.0 3.1 3.2 Grossi E & Huarte M. A lncRNA GUARDINg genome integrity[J]. Nature cell biology. 2018, 20(4):371-372.

Sequence

>gi|102724571|ref|NR_132738.1|Homo sapiens GUARDIN, long non coding RNA

000001 ACCAGGCCCC GGGGCCGCGA CGCGTCTCTC CAGCCCGGGA TCCGGGGAGC TGGGCTGTCC CCAGACCGAC GGGACAGCGG 000080
000081 CATCTCCTCC ACCTGAAAAG GAAAGAGGAC CAGTTTGCAG GACTCCGAAC TGGGCCCGCG AGATCTCCAC CTGCGCAAAA 000160
000161 CGAAAGGGCG GATTCTCCTT GGACTCACGA GGCAACCGCT CCCCGGGGTG AGAACGGGGG ACTCATTCCT CCGGCACTGG 000240
000241 GAGAAGACGA TTCTTTAGGA GGAGGACAGG GAAGCGAATG CTACCCAGAT GTCTCAGTAT ACTGGCTCGC GGCACATCGG 000320
000321 GCAAATGAAC CTATCAGATA ACAACGGCAG ATCAGATGCC TGAGCATTCA GAAGCAACAG CTGTGGAGCC CCCGTGGGTT 000400
000401 CAGAAGGCCT GGTTCCCGTC TCCAGAAGCC TGGCTCTCCT CCCTCCTGGG CCCACTACTT TGGCTTCTTG TTCCTACGTA 000480
000481 CAAGGAGTTG CGAAGAAGGC AACTCTTCCC CTCCCTGAAG CCAAAGGAAT GAAACAGACT AGGGCGGGAG AGGTGGCCAT 000560
000561 CCGTCATTAG TTGCGGCCAT CAGTAACAGC AACAGGACAC GGAACCTAAG GCTGTATCCA TCCTGGGCCC CCAGGGAAAC 000640
000641 ATCAGCGGGA GCGGTACTAA GGAAGTGCTC ATCTCTTAGA GACAAAGGCC CATGGAGGGG AACAGTAACC ATCCCCTCCC 000720
000721 AATTCAGAAA ATGTTAACAT AAGCACTTCA TTTCTCATGC AGATAACCAC ATAAGTCTAT TAATAAGAAA GAAAGAGAAA 000800
000801 GAAAAAAAAG AAAAAGGAAT CCATGCCAGC AGGGTATAGG AATTGGTCTA TAGGAGAAAG GGTCACCCAC TGAAAGGTGG 000880
000881 GCTGAATAGA ATTCCTTGCC TGGGCTTTGA GGTCCTGGCA TGGAGAAGGC TGTAGAAATG CTGGCATCAG TGGAACCCTC 000960
000961 AATAAACAGA ATTCTTGTTA AAAAAAAAAA AAAAAAAAAA AAA

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[XaPeSn6lmzD7VRsK2ZObgAAAAAI] 2019-10-14 02:32:44: Fatal exception of type "TypeError"

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