Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
August-2015 Volume 12 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
August-2015 Volume 12 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Alternatively spliced products lacking exon 12 dominate the expression of fragile X mental retardation 1 gene in human tissues

  • Authors:
    • Xianguo Fu
    • Dezhu Zheng
    • Juan Liao
    • Qingqin Li
    • Yuxiang Lin
    • Duo Zhang
    • Aizhen Yan
    • Fenghua Lan
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian 350004, P.R. China, Department of Clinical Genetics and Experimental Medicine, Fuzhou General Hospital/Clinical College of Fujian Medical University, Fuzhou, Fujian 350025, P.R. China
  • Pages: 1957-1962
    |
    Published online on: March 31, 2015
       https://doi.org/10.3892/mmr.2015.3574
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Fragile X mental retardation 1 gene (FMR1) expression is associated with fragile X syndrome (FXS) and exhibits several splicing products. However, the proportion of spliced isoforms that are expressed in different tissues remains unclear. In the present study, long‑chain reverse transcription‑polymerase chain reaction with a T cloning‑sequencing method was conducted in order to analyze the entire coding region of the FMR1 gene in human tissues. In particular, FXS‑associated tissues were analyzed, including the brain and testis. Twenty alternatively spliced isoforms were observed among 271 recombinants, including six novel ones. The isoform that consisted of the entire FMR1 coding region (ISO1) accounted for a small proportion of all isoforms. Isoforms lacking exon 12 were the most abundant. In particular, spliced isoforms ISO7 and ISO17 were the most abundant. However, their relative abundance varied between the peripheral blood cells, and the testis and brain tissues. Bioinformatic analyses suggested that exon 12 may be the sole exon undergoing positive selection. The results of the present study suggested that the mechanisms underlying alternative splicing (AS) of the FMR1 gene may be more complex. Furthermore, the functions of alternatively spliced products lacking exon 12 require further investigation. The results of the present study provide novel insights into the association between AS and the structure and function of the FMR1 gene.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Johnson JM, Castle J, Garrett-Engele P, et al: Genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays. Science. 302:2141–2144. 2003. View Article : Google Scholar : PubMed/NCBI

2 

Wang ET, Sandberg R, Luo S, et al: Alternative isoform regulation in human tissue transcriptomes. Nature. 456:470–476. 2008. View Article : Google Scholar : PubMed/NCBI

3 

Ashley CT, Sutcliffe JS, Kunst CB, et al: Human and murine FMR-1: Alternative splicing and translational initiation downstream of the CGG-repeat. Nat Genet. 4:244–251. 1993. View Article : Google Scholar : PubMed/NCBI

4 

Eichler EE, Richards S, Gibbs RA and Nelson DL: Fine structure of the human FMR1 gene. Hum Mol Genet. 2:1147–1153. 1993. View Article : Google Scholar : PubMed/NCBI

5 

Verheij C, Bakker CE, de Graaff E, et al: Characterization and localization of the FMR-1 gene product associated with fragile X syndrome. Nature. 363:722–724. 1993. View Article : Google Scholar : PubMed/NCBI

6 

Verkerk AJ, de Graaff E, De Boulle K, et al: Alternative splicing in the fragile X gene FMR1. Hum Mol Genet. 2:399–404. 1993. View Article : Google Scholar : PubMed/NCBI

7 

Sittler A, Devys D, Weber C and Mandel JL: Alternative splicing of exon 14 determines nuclear or cytoplasmic localisation of fmr1 protein isoforms. Human Mol Genet. 5:95–102. 1996. View Article : Google Scholar

8 

Blencowe BJ: Alternative splicing: new insights from global analyses. Cell. 126:37–47. 2006. View Article : Google Scholar : PubMed/NCBI

9 

Huang T, Li LY, Shen Y, Qin XB, Pang ZL and Wu GY: Alternative splicing of the FMR1 gene in human fetal brain neurons. Am J Med Genet. 64:252–255. 1996. View Article : Google Scholar : PubMed/NCBI

10 

Ding J, Huang T, Li L, Fan Y and Shen Y: Alternative splicing of the FMR1 gene in human fetal tissues. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 19:241–246. 1997.In Chinese. PubMed/NCBI

11 

Thackeray JR and Ganetzky B: Developmentally regulated alternative splicing generates a complex array of Drosophila para sodium channel isoforms. J Neurosci. 14:2569–2578. 1994.PubMed/NCBI

12 

Leparc GG and Mitra RD: A sensitive procedure to detect alternatively spliced mRNA in pooled-tissue samples. Nucleic Acids Res. 35:e1462007. View Article : Google Scholar : PubMed/NCBI

13 

Kuhn RM, Haussler D and Kent WJ: The UCSC genome browser and associated tools. Brief Bioinform. 14:144–161. 2013. View Article : Google Scholar :

14 

Tamura K, Peterson D, Peterson N, Stecher G, Nei M and Kumar S: MEGA5: Molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol. 28:2731–2739. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Poon AF, Frost SD and Pond SL: Detecting signatures of selection from DNA sequences using Datamonkey. Methods Mol Biol. 537:163–183. 2009.PubMed/NCBI

16 

Pond SL and Frost SD: Datamonkey: Rapid detection of selective pressure on individual sites of codon alignments. Bioinformatics. 21:2531–2533. 2005. View Article : Google Scholar : PubMed/NCBI

17 

Koscielny G, Le Texier V, Gopalakrishnan C, et al: ASTD: The alternative splicing and transcript diversity database. Genomics. 93:213–220. 2009. View Article : Google Scholar

18 

Takeda J, Suzuki Y, Sakate R, et al: H-DBAS: Human-transcriptome database for alternative splicing: Update 2010. Nucleic Acids Res. 38:D86–D90. 2010. View Article : Google Scholar :

19 

Ashley CT Jr, Wilkinson KD, Reines D and Warren ST: FMR1 protein: Conserved RNP family domains and selective RNA binding. Science. 262:563–566. 1993. View Article : Google Scholar : PubMed/NCBI

20 

Santoro MR, Bray SM and Warren ST: Molecular mechanisms of fragile X syndrome: A twenty-year perspective. Annu Rev Pathol. 7:219–245. 2012. View Article : Google Scholar

21 

Ascano M Jr, Mukherjee N, Bandaru P, et al: FMRP targets distinct mRNA sequence elements to regulate protein expression. Nature. 492:382–386. 2012. View Article : Google Scholar : PubMed/NCBI

22 

Denman RB and Sung YJ: Species-specific and isoform-specific RNA binding of human and mouse fragile X mental retardation proteins. Biochem Biophys Res Commun. 292:1063–1069. 2002. View Article : Google Scholar : PubMed/NCBI

23 

Xie W, Dolzhanskaya N, LaFauci G, Dobkin C and Denman RB: Tissue and developmental regulation of fragile X mental retardation 1 exon 12 and 15 isoforms. Neurobiol Dis. 35:52–62. 2009. View Article : Google Scholar : PubMed/NCBI

24 

De Boulle K, Verkerk AJ, Reyniers E, et al: A point mutation in the FMR-1 gene associated with fragile X mental retardation. Nat Genet. 3:31–35. 1993. View Article : Google Scholar : PubMed/NCBI

25 

Yang Z and Nielsen R: Estimating synonymous and nonsynonymous substitution rates under realistic evolutionary models. Mol Biol Evol. 17:32–43. 2000. View Article : Google Scholar : PubMed/NCBI

26 

Xing Y and Lee C: Alternative splicing and RNA selection pressure – evolutionary consequences for eukaryotic genomes. Nat Rev Genet. 7:499–509. 2006. View Article : Google Scholar : PubMed/NCBI

27 

Xing Y and Lee C: Evidence of functional selection pressure for alternative splicing events that accelerate evolution of protein subsequences. Proc Natl Acad Sci USA. 102:13526–13531. 2005. View Article : Google Scholar : PubMed/NCBI

28 

Filip LC and Mundy NI: Rapid evolution by positive Darwinian selection in the extracellular domain of the abundant lymphocyte protein CD45 in primates. Mol Biol Evol. 21:1504–1511. 2004. View Article : Google Scholar : PubMed/NCBI

29 

Xing Y and Lee CJ: Protein modularity of alternatively spliced exons is associated with tissue-specific regulation of alternative splicing. PLoS Genet. 1:e342005. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Fu X, Zheng D, Liao J, Li Q, Lin Y, Zhang D, Yan A and Lan F: Alternatively spliced products lacking exon 12 dominate the expression of fragile X mental retardation 1 gene in human tissues. Mol Med Rep 12: 1957-1962, 2015.
APA
Fu, X., Zheng, D., Liao, J., Li, Q., Lin, Y., Zhang, D. ... Lan, F. (2015). Alternatively spliced products lacking exon 12 dominate the expression of fragile X mental retardation 1 gene in human tissues. Molecular Medicine Reports, 12, 1957-1962. https://doi.org/10.3892/mmr.2015.3574
MLA
Fu, X., Zheng, D., Liao, J., Li, Q., Lin, Y., Zhang, D., Yan, A., Lan, F."Alternatively spliced products lacking exon 12 dominate the expression of fragile X mental retardation 1 gene in human tissues". Molecular Medicine Reports 12.2 (2015): 1957-1962.
Chicago
Fu, X., Zheng, D., Liao, J., Li, Q., Lin, Y., Zhang, D., Yan, A., Lan, F."Alternatively spliced products lacking exon 12 dominate the expression of fragile X mental retardation 1 gene in human tissues". Molecular Medicine Reports 12, no. 2 (2015): 1957-1962. https://doi.org/10.3892/mmr.2015.3574
Copy and paste a formatted citation
x
Spandidos Publications style
Fu X, Zheng D, Liao J, Li Q, Lin Y, Zhang D, Yan A and Lan F: Alternatively spliced products lacking exon 12 dominate the expression of fragile X mental retardation 1 gene in human tissues. Mol Med Rep 12: 1957-1962, 2015.
APA
Fu, X., Zheng, D., Liao, J., Li, Q., Lin, Y., Zhang, D. ... Lan, F. (2015). Alternatively spliced products lacking exon 12 dominate the expression of fragile X mental retardation 1 gene in human tissues. Molecular Medicine Reports, 12, 1957-1962. https://doi.org/10.3892/mmr.2015.3574
MLA
Fu, X., Zheng, D., Liao, J., Li, Q., Lin, Y., Zhang, D., Yan, A., Lan, F."Alternatively spliced products lacking exon 12 dominate the expression of fragile X mental retardation 1 gene in human tissues". Molecular Medicine Reports 12.2 (2015): 1957-1962.
Chicago
Fu, X., Zheng, D., Liao, J., Li, Q., Lin, Y., Zhang, D., Yan, A., Lan, F."Alternatively spliced products lacking exon 12 dominate the expression of fragile X mental retardation 1 gene in human tissues". Molecular Medicine Reports 12, no. 2 (2015): 1957-1962. https://doi.org/10.3892/mmr.2015.3574
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team