Reciprocal expression of lin‐41 and the microRNAs let‐7 and mir‐125 during mouse embryogenesis

In C. elegans, heterochronic genes control the timing of cell fate determination during development. Two heterochronic genes, let‐7 and lin‐4, encode microRNAs (miRNAs) that down‐regulate a third heterochronic gene lin‐41 by binding to complementary sites in its 3′UTR. let‐7 and lin‐4 are conserved in mammals. Here we report the cloning and sequencing of mammalian lin‐41 orthologs. We find that mouse and human lin‐41 genes contain predicted conserved complementary sites for let‐7 and the lin‐4 ortholog, mir‐125, in their 3′UTRs. Mouse lin‐41 (Mlin‐41) is temporally expressed in developing mouse embryos, most dramatically in the limb buds. Mlin‐41 is down‐regulated during mid‐embryogenesis at the time when mouse let‐7c and mir‐125 RNA levels are up‐regulated. Our results suggest that mammalian lin‐41 is temporally regulated by miRNAs in order to direct key developmental events such as limb formation. Developmental Dynamics 234:1046–1054, 2005. © 2005 Wiley‐Liss, Inc.

[1]  W. Filipowicz,et al.  Inhibition of Translational Initiation by Let-7 MicroRNA in Human Cells , 2005, Science.

[2]  A. Pasquinelli,et al.  Regulation by let-7 and lin-4 miRNAs Results in Target mRNA Degradation , 2005, Cell.

[3]  Shuang Huang,et al.  Involvement of MicroRNA in AU-Rich Element-Mediated mRNA Instability , 2005, Cell.

[4]  F. Slack,et al.  Architecture of a validated microRNA::target interaction. , 2004, Chemistry & biology.

[5]  M. Barton,et al.  MicroRNA binding sites in Arabidopsis class III HD-ZIP mRNAs are required for methylation of the template chromosome. , 2004, Developmental cell.

[6]  Michael Zuker,et al.  MicroRNA-responsive 'sensor' transgenes uncover Hox-like and other developmentally regulated patterns of vertebrate microRNA expression , 2004, Nature Genetics.

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

[8]  V. Ambros,et al.  Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation , 2004, Genome Biology.

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

[10]  Eun-Young Choi,et al.  The C. elegans microRNA let-7 binds to imperfect let-7 complementary sites from the lin-41 3'UTR. , 2004, Genes & development.

[11]  U. Kutay,et al.  Nuclear Export of MicroRNA Precursors , 2004, Science.

[12]  B. Cullen,et al.  Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. , 2003, Genes & development.

[13]  V. Kim,et al.  The nuclear RNase III Drosha initiates microRNA processing , 2003, Nature.

[14]  D. Marks,et al.  The small RNA profile during Drosophila melanogaster development. , 2003, Developmental cell.

[15]  F. Slack,et al.  The time of appearance of the C. elegans let-7 microRNA is transcriptionally controlled utilizing a temporal regulatory element in its promoter. , 2003, Developmental biology.

[16]  N. Perrimon,et al.  Coordinate regulation of small temporal RNAs at the onset of Drosophila metamorphosis. , 2003, Developmental biology.

[17]  E. Moss,et al.  Conservation of the heterochronic regulator Lin-28, its developmental expression and microRNA complementary sites. , 2003, Developmental biology.

[18]  Chiara Gamberi,et al.  The C elegans hunchback homolog, hbl-1, controls temporal patterning and is a probable microRNA target. , 2003, Developmental cell.

[19]  C. Burge,et al.  The microRNAs of Caenorhabditis elegans. , 2003, Genes & development.

[20]  C. Tickle,et al.  Patterning systems--from one end of the limb to the other. , 2003, Developmental cell.

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

[22]  G. Martin,et al.  Functions of FGF signalling from the apical ectodermal ridge in limb development , 2002, Nature.

[23]  Clifford J. Tabin,et al.  A re-examination of proximodistal patterning during vertebrate limb development , 2002, Nature.

[24]  M. A. Rector,et al.  Endogenous and Silencing-Associated Small RNAs in Plants Online version contains Web-only data. Article, publication date, and citation information can be found at www.plantcell.org/cgi/doi/10.1105/tpc.003210. , 2002, The Plant Cell Online.

[25]  T. Tuschl,et al.  Identification of Tissue-Specific MicroRNAs from Mouse , 2002, Current Biology.

[26]  T. Obinata,et al.  Molecular cloning and characterization of neural activity‐related RING finger protein (NARF): a new member of the RBCC family is a candidate for the partner of myosin V , 2001, Journal of neurochemistry.

[27]  Alessandro Guffanti,et al.  The tripartite motif family identifies cell compartments , 2001, The EMBO journal.

[28]  R. Wharton,et al.  Drosophila Brain Tumor is a translational repressor. , 2001, Genes & development.

[29]  B. Reinhart,et al.  Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA , 2000, Nature.

[30]  S. Rosengren,et al.  Gene encoding a new RING-B-box-Coiled-coil protein is mutated in mulibrey nanism , 2000, Nature Genetics.

[31]  F. Slack,et al.  The lin-41 RBCC gene acts in the C. elegans heterochronic pathway between the let-7 regulatory RNA and the LIN-29 transcription factor. , 2000, Molecular cell.

[32]  B. Reinhart,et al.  The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans , 2000, Nature.

[33]  V. Ambros,et al.  The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. , 1999, Developmental biology.

[34]  S. Vincent,et al.  Cloning and Characterization of a Novel RING Finger Protein That Interacts with Class V Myosins* , 1999, The Journal of Biological Chemistry.

[35]  V. Ambros,et al.  The timing of lin-4 RNA accumulation controls the timing of postembryonic developmental events in Caenorhabditis elegans. , 1999, Developmental biology.

[36]  F. Slack,et al.  A novel repeat domain that is often associated with RING finger and B-box motifs. , 1998, Trends in biochemical sciences.

[37]  Thomas L. Madden,et al.  Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. , 1997, Nucleic acids research.

[38]  V. Ambros,et al.  The Cold Shock Domain Protein LIN-28 Controls Developmental Timing in C. elegans and Is Regulated by the lin-4 RNA , 1997, Cell.

[39]  G. Ruvkun,et al.  A bulged lin-4/lin-14 RNA duplex is sufficient for Caenorhabditis elegans lin-14 temporal gradient formation. , 1996, Genes & development.

[40]  P. Freemont,et al.  Does this have a familiar RING? , 1996, Trends in biochemical sciences.

[41]  P. Freemont,et al.  The solution structure of the RING finger domain from the acute promyelocytic leukaemia proto‐oncoprotein PML. , 1995, The EMBO journal.

[42]  G. Ruvkun,et al.  Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans , 1993, Cell.

[43]  V. Ambros,et al.  The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14 , 1993, Cell.

[44]  P. Freemont.  The RING Finger , 1993 .

[45]  S. Heyningen.  The ring on a finger , 1991, Nature.

[46]  H. Horvitz,et al.  Heterochronic mutants of the nematode Caenorhabditis elegans. , 1984, Science.

[47]  Martin Chalfie,et al.  Mutations that lead to reiterations in the cell lineages of C. elegans , 1981, Cell.

[48]  H. Lipkin.  Where is the ?c? , 1978 .

[49]  D. SUMMERBELL,et al.  Positional Information in Chick Limb Morphogenesis , 1973, Nature.

[50]  P. Freemont.  The RING finger. A novel protein sequence motif related to the zinc finger. , 1993, Annals of the New York Academy of Sciences.