An Evolutionarily Conserved Mechanism for MicroRNA-223 Expression Revealed by MicroRNA Gene Profiling

Many microRNAs (miRNAs) are evolutionarily conserved and have intriguing expression patterns. Tissue and/or time-specific expressions of some miRNAs are presumably controlled by unique cis-acting regulatory elements that coevolved with the miRNA sequences. Exploiting bioinformatics, we identified several miRNAs whose primary transcripts could be regulated by conserved genomic elements proximal to their transcription start sites. Such miRNAs include microRNA-223 (miR-223), which is reportedly controlled by a unique regulatory mechanism during granulopoiesis. Here, we define a mechanism distinct from that previously proposed to regulate miR-223 expression. We find that the mir-223 gene resembles a "myeloid gene" and might be driven by the myeloid transcription factors, PU.1 and C/EBPs. This mechanism is specified by the conserved proximal cis-regulatory element and might be common among different species. Hence, it needs to be considered that two distinct mechanisms that would play critical roles in myeloid functions and differentiation are actually concerned with the regulation of miR-223.

[1]  Jin-Wu Nam,et al.  Genomics of microRNA. , 2006, Trends in genetics : TIG.

[2]  V. Kim.  MicroRNA biogenesis: coordinated cropping and dicing , 2005, Nature Reviews Molecular Cell Biology.

[3]  D. Bartel,et al.  MicroRNAs Modulate Hematopoietic Lineage Differentiation , 2004, Science.

[4]  Stuart H. Orkin,et al.  Hematopoiesis and stem cells: plasticity versus developmental heterogeneity , 2002, Nature Immunology.

[5]  V. Ambros,et al.  An Extensive Class of Small RNAs in Caenorhabditis elegans , 2001, Science.

[6]  M. Plumb,et al.  C/EBP, NF-kappa B, and c-Ets family members and transcriptional regulation of the cell-specific and inducible macrophage inflammatory protein 1 alpha immediate-early gene , 1993, Molecular and cellular biology.

[7]  C. Darimont,et al.  C/EBPalpha regulates human adiponectin gene transcription through an intronic enhancer. , 2005, Diabetes.

[8]  S. R. Himes,et al.  A highly conserved c‐fms gene intronic element controls macrophage‐specific and regulated expression , 2001, Journal of leukocyte biology.

[9]  Sam Griffiths-Jones,et al.  The microRNA Registry , 2004, Nucleic Acids Res..

[10]  E. Birney,et al.  Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs , 2002, Nature.

[11]  Piero Carninci,et al.  High-efficiency full-length cDNA cloning. , 1999, Methods in enzymology.

[12]  Jiang Zhu,et al.  Hematopoietic cytokines, transcription factors and lineage commitment , 2002, Oncogene.

[13]  T. Asano,et al.  PI3K-mediated negative feedback regulation of IL-12 production in DCs , 2002, Nature Immunology.

[14]  V. Kim,et al.  MicroRNA maturation: stepwise processing and subcellular localization , 2002, The EMBO journal.

[15]  Piero Carninci,et al.  Normalization and subtraction of cap-trapper-selected cDNAs to prepare full-length cDNA libraries for rapid discovery of new genes. , 2000, Genome research.

[16]  H. Lodish,et al.  MicroRNAs as regulators of mammalian hematopoiesis. , 2005, Seminars in immunology.

[17]  S. Batalov,et al.  Antisense Transcription in the Mammalian Transcriptome , 2005, Science.

[18]  B. Venkatesh,et al.  Comparative genomics using fugu: a tool for the identification of conserved vertebrate cis-regulatory elements. , 2005, BioEssays : news and reviews in molecular, cellular and developmental biology.

[19]  T. Graf,et al.  A transcription factor party during blood cell differentiation. , 1998, Current opinion in genetics & development.

[20]  Daniel G Tenen,et al.  ATRA resolves the differentiation block in t(15;17) acute myeloid leukemia by restoring PU.1 expression. , 2004, Blood.

[21]  Alessandro Fatica,et al.  A Minicircuitry Comprised of MicroRNA-223 and Transcription Factors NFI-A and C/EBPα Regulates Human Granulopoiesis , 2005, Cell.

[22]  L. Lim,et al.  An Abundant Class of Tiny RNAs with Probable Regulatory Roles in Caenorhabditis elegans , 2001, Science.

[23]  C. Bult,et al.  Functional annotation of a full-length mouse cDNA collection , 2001, Nature.

[24]  Daniel G Tenen,et al.  C/EBPβ: a major PML–RARA‐responsive gene in retinoic acid‐induced differentiation of APL cells , 2003, The EMBO journal.

[25]  John Bracht,et al.  MicroRNAs: a developing story. , 2005, Current opinion in genetics & development.

[26]  R. Aharonov,et al.  Identification of hundreds of conserved and nonconserved human microRNAs , 2005, Nature Genetics.

[27]  D. Bartel,et al.  MicroRNA-Directed Cleavage of HOXB8 mRNA , 2004, Science.

[28]  D. Bartel,et al.  Micromanagers of gene expression: the potentially widespread influence of metazoan microRNAs , 2004, Nature Reviews Genetics.

[29]  Sanghyuk Lee,et al.  MicroRNA genes are transcribed by RNA polymerase II , 2004, The EMBO journal.

[30]  A. Friedman.  Transcriptional regulation of granulocyte and monocyte development , 2002, Oncogene.

[31]  S. Salzberg,et al.  The Transcriptional Landscape of the Mammalian Genome , 2005, Science.

[32]  J. Licht,et al.  Transcription factors, normal myeloid development, and leukemia. , 1997, Blood.

[33]  A. Rosmarin,et al.  Transcriptional regulation in myelopoiesis: Hematopoietic fate choice, myeloid differentiation, and leukemogenesis. , 2005, Experimental hematology.

[34]  T. Tuschl,et al.  Identification of Novel Genes Coding for Small Expressed RNAs , 2001, Science.

[35]  D. Bartel.  MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[36]  D J Lipman,et al.  Making (anti)sense of non-coding sequence conservation. , 1997, Nucleic acids research.