Home LiteratureArticle Details
PMID: 16882971 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Extensive post-transcriptional regulation of microRNAs and its implications for cancer.

Genes & development ·Vol. 20 ·No. 16 ·2006-08-15 ·Pages 2202-7

Thomson JM, Newman M, Parker JS, Morin-Kensicki EM, Wright T, Hammond SM

Abstract

MicroRNAs (miRNAs) are short, noncoding RNAs that post-transcriptionally regulate gene expression. While hundreds of mammalian miRNA genes have been identified, little is known about the pathways that regulate the production of active miRNA species. Here we show that a large fraction of miRNA genes are regulated post-transcriptionally. During early mouse development, many miRNA primary transcripts, including the Let-7 family, are present at high levels but are not processed by the enzyme Drosha. An analysis of gene expression in primary tumors indicates that the widespread down-regulation of miRNAs observed in cancer is due to a failure at the Drosha processing step. These data uncover a novel regulatory step in miRNA function and provide a mechanism for miRNA down-regulation in cancer.

MeSH Terms
Animals Blotting, Northern Cell Line Cell Line, Tumor Down-Regulation Embryo, Mammalian/metabolism Embryonic Development Female Mice MicroRNAs/genetics,metabolism Neoplasms/genetics,metabolism Oligonucleotide Array Sequence Analysis RNA Processing, Post-Transcriptional Reverse Transcriptase Polymerase Chain Reaction Ribonuclease III/metabolism Stem Cells/metabolism Teratocarcinoma/genetics,metabolism Up-Regulation
Chemicals
MicroRNAs Drosha protein, mouse Ribonuclease III
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Thomson J Michael
Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Newman Martin
Parker Joel S
Morin-Kensicki Elizabeth M
Wright Tricia
Hammond Scott M
References (33)
33 references, click to expand
  1. Human RISC couples microRNA biogenesis and posttranscriptional gene silencing.
    Cell. 2005 Nov 18;123(4):631-40 PMID: 16271387
  2. microPrimer: the biogenesis and function of microRNA.
    Development. 2005 Nov;132(21):4645-52 PMID: 16224044
  3. A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis.
    Cell. 2005 Dec 2;123(5):819-31 PMID: 16325577
  4. A human, ATP-independent, RISC assembly machine fueled by pre-miRNA.
    Genes Dev. 2005 Dec 15;19(24):2979-90 PMID: 16357216
  5. In situ detection of miRNAs in animal embryos using LNA-modified oligonucleotide probes.
    Nat Methods. 2006 Jan;3(1):27-9 PMID: 16369549
  6. miRBase: microRNA sequences, targets and gene nomenclature.
    Nucleic Acids Res. 2006 Jan 1;34(Database issue):D140-4 PMID: 16381832
  7. Modulation of microRNA processing and expression through RNA editing by ADAR deaminases.
    Nat Struct Mol Biol. 2006 Jan;13(1):13-21 PMID: 16369484
  8. The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation.
    Nat Genet. 2006 Feb;38(2):228-33 PMID: 16380711
  9. Post-transcriptional regulation of microRNA expression.
    RNA. 2006 Jul;12(7):1161-7 PMID: 16738409
  10. Facile means for quantifying microRNA expression by real-time PCR.
    Biotechniques. 2005 Oct;39(4):519-25 PMID: 16235564
  11. MicroRNA function in animal development.
    FEBS Lett. 2005 Oct 31;579(26):5911-22 PMID: 16111679
  12. Identification and characterization of small RNAs involved in RNA silencing.
    FEBS Lett. 2005 Oct 31;579(26):5830-40 PMID: 16153643
  13. An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells.
    Nature. 2000 Mar 16;404(6775):293-6 PMID: 10749213
  14. A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA.
    Science. 2001 Aug 3;293(5531):834-8 PMID: 11452083
  15. Multiclass cancer diagnosis using tumor gene expression signatures.
    Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15149-54 PMID: 11742071
  16. The time of appearance of the C. elegans let-7 microRNA is transcriptionally controlled utilizing a temporal regulatory element in its promoter.
    Dev Biol. 2003 Jul 15;259(2):364-79 PMID: 12871707
  17. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival.
    Cancer Res. 2004 Jun 1;64(11):3753-6 PMID: 15172979
  18. Human embryonic stem cells express a unique set of microRNAs.
    Dev Biol. 2004 Jun 15;270(2):488-98 PMID: 15183728
  19. Argonaute2 is the catalytic engine of mammalian RNAi.
    Science. 2004 Sep 3;305(5689):1437-41 PMID: 15284456
  20. Trans-splicing and polyadenylation of let-7 microRNA primary transcripts.
    RNA. 2004 Oct;10(10):1586-94 PMID: 15337850
  21. Smooth muscle actin expression during P19 embryonal carcinoma differentiation in cell culture.
    J Cell Physiol. 1990 Jan;142(1):89-98 PMID: 2404996
  22. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14.
    Cell. 1993 Dec 3;75(5):843-54 PMID: 8252621
  23. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans.
    Cell. 1993 Dec 3;75(5):855-62 PMID: 8252622
  24. Accumulation of miR-155 and BIC RNA in human B cell lymphomas.
    Proc Natl Acad Sci U S A. 2005 Mar 8;102(10):3627-32 PMID: 15738415
  25. RAS is regulated by the let-7 microRNA family.
    Cell. 2005 Mar 11;120(5):635-47 PMID: 15766527
  26. A custom microarray platform for analysis of microRNA gene expression.
    Nat Methods. 2004 Oct;1(1):47-53 PMID: 15782152
  27. A microRNA polycistron as a potential human oncogene.
    Nature. 2005 Jun 9;435(7043):828-33 PMID: 15944707
  28. MicroRNA expression profiles classify human cancers.
    Nature. 2005 Jun 9;435(7043):834-8 PMID: 15944708
  29. c-Myc-regulated microRNAs modulate E2F1 expression.
    Nature. 2005 Jun 9;435(7043):839-43 PMID: 15944709
  30. MicroRNA biogenesis: coordinated cropping and dicing.
    Nat Rev Mol Cell Biol. 2005 May;6(5):376-85 PMID: 15852042
  31. MicroRNA expression in zebrafish embryonic development.
    Science. 2005 Jul 8;309(5732):310-1 PMID: 15919954
  32. Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis.
    Nature. 2005 Jul 14;436(7048):214-20 PMID: 15951802
  33. Reciprocal expression of lin-41 and the microRNAs let-7 and mir-125 during mouse embryogenesis.
    Dev Dyn. 2005 Dec;234(4):1046-54 PMID: 16247770
Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1444406
Published
2006-08-15
Epub
2006-00-01
Pages
2202-7
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC1553203
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.1444406 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2