2008-1-2 17:31:00

G & D:三篇文章揭示miRNA重要发现

原文二:

GENES & DEVELOPMENT 22:8-13, 2008

A single Hox locus in Drosophila produces functional microRNAs from opposite DNA strands

Alexander Stark1,2,6,8, Natascha Bushati3,6, Calvin H. Jan4, Pouya Kheradpour1,2, Emily Hodges5, Julius Brennecke5, David P. Bartel4, Stephen M. Cohen3,7, and Manolis Kellis1,9

1 Broad Institute of Massachussetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02141, USA; 2 Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA; 3 European Molecular Biology Laboratory, 69117 Heidelberg, Germany; 4 Department of Biology, Howard Hughes Medical Institute and Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology Cambridge, Massachusetts 02139, USA; 5 Watson School of Biological Sciences and Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA

MicroRNAs (miRNAs) are ~22-nucleotide RNAs that are processed from characteristic precursor hairpins and pair to sites in messages of protein-coding genes to direct post-transcriptional repression. Here, we report that the miRNA iab-4 locus in the Drosophila Hox cluster is transcribed convergently from both DNA strands, giving rise to two distinct functional miRNAs. Both sense and antisense miRNA products target neighboring Hox genes via highly conserved sites, leading to homeotic transformations when ectopically expressed. We also report sense/antisense miRNAs in mouse and find antisense transcripts close to many miRNAs in both flies and mammals, suggesting that additional sense/antisense pairs exist.

[Keywords: Drosophila; miR-iab-4; Hox; antisense miRNAs]]

Received September 6, 2007; revised version accepted November 2, 2007.

6 This authors contributed equally to this work.

7 Present address: Temasek Life Sciences Laboratory, The National University of Singapore, Singapore 117604.

8 Corresponding authors.

E-MAIL alex.stark@mit.edu ; FAX (617) 253-7512.

原文三:

GENES & DEVELOPMENT 22:14-19, 2008

MicroRNAs in the Drosophila bithorax complex

Welcome Bender1

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA

The iab-4 noncoding RNA from the Drosophila bithorax complex is the substrate for a microRNA (miRNA). Gene conversion was used to delete the hairpin precursor of this miRNA; flies homozygous for this deletion are sterile. Surprisingly, this mutation complements with rearrangement breakpoint mutations that disrupt the iab-4 RNA but fails to complement with breaks mapping in the iab-5 through iab-7 regulatory regions. These breaks disrupt the iab-8 RNA, transcribed from the opposite strand. This iab-8 RNA also encodes a miRNA, detected on Northern blots, derived from the hairpin complementary to the iab-4 precursor hairpin. Ultrabithorax is a target of both miRNAs, although its repression is subtle in both cases.

[Keywords: Ultrabithorax; noncoding RNA; abdominal-A; iab-8 RNA]]

Received September 10, 2007; revised version accepted November 9, 2007.

1 Correspondence.

PHONE (617) 432-1906; FAX (617) 738-0516.

PHONE (617) 432-1906; FAX (617) 738-0516.


附:
Eric C. Lai

Education

1999 Ph.D. in Biology, University of California at San Diego
1993 B.A., magna cum laude in Biochemistry, Harvard University

Research and Professional Experience

2005 Assistant Member, Department of Developmental Biology
Memorial Sloan-Kettering Cancer Center, New York, NY
2005 Assistant Professor, Program in Cell Biology and Genetics
Weill Cornell Medical School, New York, NY
1999-2005 Postdoctoral fellow, HHMI/Department of Molecular and Cell Biology
University of California at Berkeley, Berkeley, CA
1. "Regulation of the Notch pathway by ubiquitin ligases"
2. "Genomewide analysis of Drosophila microRNA function"
Dr. Gerald M. Rubin, postdoctoral advisor
1993-1999 Predoctoral fellow, Department of Biology
University of California at San Diego, La Jolla, CA
"Pattern formation during Drosophila sensory organ development"
Dr. James W. Posakony, graduate thesis advisor
1992-1993 Undergraduate thesis research, Department of Molecular Biology
Massachusetts General Hospital/Harvard Medical School, Boston, MA
"Spatial expression of ceh-20, a C. elegans PBX-class homeobox gene"
Dr. Gary Ruvkun, undergraduate thesis advisor

Selected Awards and Fellowships:

2005 Career Award in the Biomedical Sciences, Burroughs Wellcome Fund
2004-2006 Special Fellow of the Leukemia and Lymphoma Society
2000-2003 Fellow of the Damon Runyon Cancer Research Foundation
2000 Jane Coffin Childs Memorial Fund for Medical Research Fellowship (declined)
2000 Larry Sandler Memorial Award for Drosophila Research, Finalist
1993-1999 Fellow of the Lucille P. Markey Charitable Trust
1993 Phi Beta Kappa, Harvard College
1991 John Harvard Scholarship
1989 National Merit Scholarship

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