Jump to content

User:Jkrodg/sandbox

From Wikipedia, the free encyclopedia

An Error has occurred retrieving Wikidata item for infobox

Location of MIAT within Chromosome 22

MIAT (myocardial infarction associated transcript), also known as RNCR2 (retinal non-coding RNA 2) or Gomafu, is a long non-coding RNA. Single nucleotide polymorphisms (SNPs) in MIAT are associated with a risk of myocardial infarction.[1] It is expressed in neurons, and located in the nucleus.[2] It plays a role in the regulation of retinal cell fate specification.[3] Crea and collaborators have shown that MIAT is highly up-regulated in aggressive prostate cancer samples,[4] raising the possibility that this gene plays a role in cancer progression.

Structure

[edit]

The myocardial infarction associated transcript gene is located on Chromosome 22 and its size is 30,051 bases.[5]As it has been stated, MIAT is also known as  gomafu.[6] Gomafu is a word in Japanese that means “spotted pattern”.[6] It is after all distributed in the nucleoplasm in a spotted pattern. Its orientation is a plus strand[5].It has five exons and is likely to be a functional RNA, as MIAT hasn’t been shown to encode any translational product[5]. It is expressed in the neurons and located in the nucleus[6].

The gene encodes a spliced, long non-coding RNA.[5]

The gene is found not only in humans, but also in mice and rats.[6] Orthologs are present in syntenic positions of frog and chicken.[7] It is also found that all gomafu RNA contain tandem repeats of UACUAAC that binds to SPF1, which is a splicing factor.[6]

MIAT was originally discovered as long intergenic noncoding RNAs quite enriched in specific neurons in mouse retina and later more widely expressed in the nervous system and cultured neurons, where it specifies cell identity.[6] The gomafu RNA is also very insoluble.[6] It is also enriched in PolyA+ and there are putative polyadenylation signals found at the 3’ end of this gene. The presence of a PolyA tail and multiple exons and introns fulfills the feature of mRNAs transcribed by RNA polymerase II. The stability of the gene is not significantly different from β-actin mRNA.[6]

Function in Pathology

[edit]

Myocardial Infarction

[edit]

Myocardial infarction is more commonly known as a heart attack. It is the irreversible death of the heart muscle due to prolonged obstruction of blood supply to the organ. Case-controlled large scale studies utilizing Single Nucleotide Polymorphisms(SNPs) throughout the genome demonstrated that altered expression at 6 SNPs in the MIAT gene might confer genetic susceptibility to myocardial infarctions. MIAT has been demonstrated to encode a nonfunctional RNA. Although the exact function of MIAT is still unclear, knowledge of some of the genetic factors that contribute to the pathogenesis of myocardial infarction can lend itself to better diagnosis, prevention, and treatment. Despite all that has been discovered about MIAT,  a causal link between MIAT and myocardial infarctions has not yet been demonstrated [8].

Model of the molecular mechanism of Gomafu

Additionally, one study demonstrated that expression levels of MIAT are shown to change in peripheral blood cells of patients with acute myocardial infarction. MIAT is positively associated with lymphocytes, and negatively associated with neutrophils and platelets. Smoking was a cardiovascular risk that MIAT was associated with. MIAT was also found to be a significant predictor of left ventricular dysfunction[9]. MIAT has various genotypes of SNPs and it is possible that only one of them relates to heart disease[10].

Schizophrenia

[edit]

The long non-coding RNA(lncRNA) MIAT is located in the same chromosomal region which is linked to Schizophrenia (SZ) 22Q12.1.[11]

MIAT is upregulated in the nucleus accumbens of cocaine and heroin users.[12][13] The nucleus accumbens is a region involved in behavior and addiction,[14] suggesting that dysregulation of MIAT can influence behavior.

It is well accepted that alternative splicing has a role in SZ pathology.[15]  MIAT is associated with alternative splicing through its interaction with splicing factor 1(SF1)[7] and with genes DISC1 and ERBB4.[16] MIAT binds directly to the splicing regulator quaking homolog (QKI) and serine/arginine-rich splicing factor 1 (SRSF1).[17] QKI gene expression is decreased in specific brain regions in SZ [18][19] and it has been proposed to be involved in SZ.[20][21]

Post -mortem SZ brains have upregulated expression of both DISC1 and ERBB4.[17]

Overexpression of MIAT in human-induced pluripotent stem cell (HiPSC)-derived neurons shows a significant decrease in expression of both DISC1 and ERBB4 and their alternative spliced variants.[17] This is opposite to the upregulated expression seen in SZ patient brains.[17]

ASO mediated knockdown of MIAT in (HiPSC)-derived neurons increase the expression of both DISC1 and ERBB4 splice variants, but not their unspliced transcripts.[17] This is almost exactly matching the aberrant splicing pattern seen in post-mortem SZ patient’s brains.[17]

These results suggests that loss of function mutations or decreased expression of MIAT is involved in driving aberrant cortical splicing patterns observed in SZ post-mortem brains.[17]

Other Pathologies

[edit]

MIAT up-regulation and down-regulation has been linked to various types of cancer and other pathologies.

In a study of glioblastoma multiforme, increased expression of MIAT was linked to increased survival rates.[22] In addition, the glioma cells were found to how significantly down-regulated MIAT.[22] The role of MIAT in lymphocytic leukemia is very different from that of glioblastoma. In certain aggressive cell lines of chronic lymphocytic leukemias, MIAT is upregulated and depends on the presence of a transcriptional regulator, OCT4.[23] OCT4 serves a a positive regulator of MIAT transcription and as of now is the only known regulator. However, analysis of relative concentrations of MIAT and OCT4 have indicated that other regulatory factors are in play.[23]

Beyond its role in cancer, MIAT misexpression has also been linked to neurovascular dysfunction.[24]

References

[edit]
  1. ^ Ishii N, Ozaki K, Sato H, et al. (2006). "Identification of a novel non-coding RNA, MIAT, that confers risk of myocardial infarction". J. Hum. Genet. 51 (12): 1087–99. doi:10.1007/s10038-006-0070-9. PMID 17066261.
  2. ^ Sone M, Hayashi T, Tarui H, Agata K, Takeichi M, Nakagawa S (August 2007). "The mRNA-like noncoding RNA Gomafu constitutes a novel nuclear domain in a subset of neurons". J. Cell. Sci. 120 (Pt 15): 2498–506. doi:10.1242/jcs.009357. PMID 17623775.
  3. ^ Rapicavoli NA, Poth EM, Blackshaw S (2010). "The long noncoding RNA RNCR2 directs mouse retinal cell specification". BMC Dev. Biol. 10: 49. doi:10.1186/1471-213X-10-49. PMC 2876091. PMID 20459797.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  4. ^ Vausort, Mélanie; Wagner, Daniel R.; Devaux, Yvan (2014-09-12). "Long Noncoding RNAs in Patients With Acute Myocardial InfarctionNovelty and Significance". Circulation Research. 115 (7): 668–677. doi:10.1161/CIRCRESAHA.115.303836. ISSN 0009-7330.
  5. ^ a b c d Ishii, Nobuaki; Ozaki, Kouichi; Sato, Hiroshi; Mizuno, Hiroya; Saito, Susumu; Takahashi, Atsushi; Miyamoto, Yoshinari; Ikegawa, Shiro; Kamatani, Naoyuki (2006-10-26). "Identification of a novel non-coding RNA, MIAT, that confers risk of myocardial infarction". Journal of Human Genetics. 51 (12): 1087–1099. doi:10.1007/s10038-006-0070-9. ISSN 1434-5161.
  6. ^ a b c d e f g h Sone, Masamitsu; Hayashi, Tetsutaro; Tarui, Hiroshi; Agata, Kiyokazu; Takeichi, Masatoshi; Nakagawa, Shinichi (2007-08-01). "The mRNA-like noncoding RNA Gomafu constitutes a novel nuclear domain in a subset of neurons". J Cell Sci. 120 (15): 2498–2506. doi:10.1242/jcs.009357. ISSN 0021-9533.
  7. ^ a b Tsuiji, Hitomi; Yoshimoto, Rei; Hasegawa, Yuko; Furuno, Masaaki; Yoshida, Minoru; Nakagawa, Shinichi (2011-05-01). "Competition between a noncoding exon and introns: Gomafu contains tandem UACUAAC repeats and associates with splicing factor-1". Genes to Cells. 16 (5): 479–490. doi:10.1111/j.1365-2443.2011.01502.x. ISSN 1365-2443.
  8. ^ Ishii, Nobuaki; Ozaki, Kouichi; Sato, Hiroshi; Mizuno, Hiroya; Saito, Susumu; Takahashi, Atsushi; Miyamoto, Yoshinari; Ikegawa, Shiro; Kamatani, Naoyuki (2006-10-26). "Identification of a novel non-coding RNA, MIAT, that confers risk of myocardial infarction". Journal of Human Genetics. 51 (12): 1087–1099. doi:10.1007/s10038-006-0070-9. ISSN 1434-5161.
  9. ^ Vausort, Mélanie; Wagner, Daniel R.; Devaux, Yvan (2014-09-12). "Long Noncoding RNAs in Patients With Acute Myocardial InfarctionNovelty and Significance". Circulation Research. 115 (7): 668–677. doi:10.1161/CIRCRESAHA.115.303836. ISSN 0009-7330.
  10. ^ Tsunoda, Tatsuhiko; Lathrop, G. Mark; Sekine, Akihiro; Yamada, Ryo; Takahashi, Atsushi; Ohnishi, Yozo; Tanaka, Toshihiro; Nakamura, Yusuke (2004-08-01). "Variation of gene-based SNPs and linkage disequilibrium patterns in the human genome". Human Molecular Genetics. 13 (15): 1623–1632. doi:10.1093/hmg/ddh177. ISSN 0964-6906.
  11. ^ "Significant linkage to chromosome 22q for exploratory eye movement dysfunction in schizophrenia". American Journal of Medical Genetics. 123B.
  12. ^ Albertson, Dawn N.; Schmidt, Carl J.; Kapatos, Gregory; Bannon, Michael J. (2006-05-03). "Distinctive Profiles of Gene Expression in the Human Nucleus Accumbens Associated with Cocaine and Heroin Abuse". Neuropsychopharmacology. 31 (10): 2304–2312. doi:10.1038/sj.npp.1301089. ISSN 0893-133X.
  13. ^ Michelhaugh, Sharon K.; Lipovich, Leonard; Blythe, Jason; Jia, Hui; Kapatos, Gregory; Bannon, Michael J. (2011-02-01). "Mining Affymetrix microarray data for long non-coding RNAs: altered expression in the nucleus accumbens of heroin abusers". Journal of Neurochemistry. 116 (3): 459–466. doi:10.1111/j.1471-4159.2010.07126.x. ISSN 1471-4159.
  14. ^ Di Chiara, Gaetano; Bassareo, Valentina; Fenu, Sandro; De Luca, Maria Antonietta; Spina, Liliana; Cadoni, Cristina; Acquas, Elio; Carboni, Ezio; Valentini, Valentina (2004-01-01). "Dopamine and drug addiction: the nucleus accumbens shell connection". Neuropharmacology. Frontiers in Addiction Research: Celebrating the 30th Anniversary of the National Institute on Drug Abuse. 47, Supplement 1: 227–241. doi:10.1016/j.neuropharm.2004.06.032.
  15. ^ Morikawa, Tomomi; Manabe, Takayuki (2010-12-01). "Aberrant regulation of alternative pre-mRNA splicing in schizophrenia". Neurochemistry International. 57 (7): 691–704. doi:10.1016/j.neuint.2010.08.012.
  16. ^ Law, Amanda J.; Kleinman, Joel E.; Weinberger, Daniel R.; Weickert, Cynthia Shannon (2007-01-15). "Disease-associated intronic variants in the ErbB4 gene are related to altered ErbB4 splice-variant expression in the brain in schizophrenia". Human Molecular Genetics. 16 (2): 129–141. doi:10.1093/hmg/ddl449. ISSN 0964-6906.
  17. ^ a b c d e f g Barry, G; Briggs, J A; Vanichkina, D P; Poth, E M; Beveridge, N J; Ratnu, V S; Nayler, S P; Nones, K; Hu, J. "The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing". Molecular Psychiatry. 19 (4): 486–494. doi:10.1038/mp.2013.45.
  18. ^ Haroutunian, Vahram; Katsel, Pavel; Dracheva, Stella; Davis, Kenneth L. (2006-10-01). "The Human Homolog of the QKI Gene Affected in the Severe Dysmyelination "Quaking" Mouse Phenotype: Downregulated in Multiple Brain Regions in Schizophrenia". American Journal of Psychiatry. 163 (10): 1834–1837. doi:10.1176/ajp.2006.163.10.1834. ISSN 0002-953X.
  19. ^ MCCULLUMSMITH, R; GUPTA, D; BENEYTO, M; KREGER, E; HAROUTUNIAN, V; DAVIS, K; MEADORWOODRUFF, J. "Expression of transcripts for myelination-related genes in the anterior cingulate cortex in schizophrenia☆". Schizophrenia Research. 90 (1–3): 15–27. doi:10.1016/j.schres.2006.11.017. PMC 1880890. PMID 17223013.
  20. ^ Åberg, Karolina; Saetre, Peter; Jareborg, Niclas; Jazin, Elena (2006-05-09). "Human QKI, a potential regulator of mRNA expression of human oligodendrocyte-related genes involved in schizophrenia". Proceedings of the National Academy of Sciences. 103 (19): 7482–7487. doi:10.1073/pnas.0601213103. ISSN 0027-8424.
  21. ^ Åberg, Karolina; Saetre, Peter; Lindholm, Eva; Ekholm, Birgit; Pettersson, Ulf; Adolfsson, Rolf; Jazin, Elena (2006-01-05). "Human QKI, a new candidate gene for schizophrenia involved in myelination". American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. 141B (1): 84–90. doi:10.1002/ajmg.b.30243. ISSN 1552-485X.
  22. ^ a b Zhang, Xiao-Qin; Sun, Stella; Lam, Kwok-Fai; Kiang, Karrie Mei-Yee; Pu, Jenny Kan-Suen; Ho, Amy Shuk-Wai; Lui, Wai-Man; Fung, Ching-Fai; Wong, Thian-Sze. "A long non-coding RNA signature in glioblastoma multiforme predicts survival". Neurobiology of Disease. 58: 123–131. doi:10.1016/j.nbd.2013.05.011.
  23. ^ a b Sattari, Arash; Siddiqui, Hasan; Moshiri, Farzaneh; Ngankeu, Apollinaire; Nakamura, Tatsuya; Kipps, Thomas J.; Croce, Carlo M. (2016-08-05). "Upregulation of long noncoding RNA MIAT in aggressive form of chronic lymphocytic leukemias". Oncotarget. 7 (34). doi:10.18632/oncotarget.11099. ISSN 1949-2553.
  24. ^ Jiang, Qin; Shan, Kun; Qun-Wang, Xiao; Zhou, Rong-Mei; Yang, Hong; Liu, Chang; Li, Yu-Jie; Yao, Jin; Li, Xiu-Miao (2016-07-06). "Long non-coding RNA-MIAT promotes neurovascular remodeling in the eye and brain". Oncotarget. 7 (31). doi:10.18632/oncotarget.10434. ISSN 1949-2553.
Retrieved from "https://en.wikipedia.org/w/index.php?title=User:Jkrodg/sandbox&oldid=749695070"