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Phillip A. Sharp

Bio: Phillip A. Sharp is an academic researcher from Massachusetts Institute of Technology. The author has contributed to research in topics: RNA & RNA splicing. The author has an hindex of 172, co-authored 614 publications receiving 117126 citations. Previous affiliations of Phillip A. Sharp include McGovern Institute for Brain Research & Medical Research Council.
Topics: RNA, RNA splicing, Gene, Transcription (biology), DNA


Papers
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Journal ArticleDOI
08 Apr 1988-Cell
TL;DR: A family of related multisubunit CCAAT-binding proteins that are composed of heterologous subunits are proposed that are related to each other and to the adenovirus origin of replication and is required for the initiation ofadenoviral replication.

596 citations

Journal ArticleDOI
17 Jun 1994-Cell

578 citations

Journal ArticleDOI
16 Oct 1986-Nature
TL;DR: Two species of nuclear proteins which bind specifically to an octamer sequence, ATTTGCAT, are detected using an electrophoretic mobility shift assay to identify DNA binding proteins.
Abstract: Immunoglobulin gene promoters are active only in lymphoid cells and this tissue-specific activity requires an octamer sequence, ATTTGCAT. Paradoxically, this same octamer motif seems to be a transcriptional control element in promoters which are active in all tissues. Using an electrophoretic mobility shift assay to identify DNA binding proteins, we have now detected two species of nuclear proteins which bind specifically to this octamer. One previously characterized form (NF-A1) was found in all cell lines tested while the other form (NF-A2) was restricted to lymphoid cell lines. NF-A2 was found in cell lines representing all stages of B-cell differentiation and in half of the T-lymphoma cell lines tested. The identification of a lymphoid-specific octamer binding protein may account for the lymphoid-specific activity of immunoglobulin promoters.

575 citations

Journal ArticleDOI
TL;DR: The splicing of precursors to mRNAs occurs in two steps, both involving single transesterification reactions (Fig. 1). The first step generates a 2′-5′ bond at the branch site upstream of the 3′ splice site and a free 3′ hydroxyl group on the 5′ exon.
Abstract: The splicing of precursors to mRNAs occurs in two steps, both involving single transesterification reactions (Fig. 1). The first step generates a 2′ – 5′ bond at the branch site upstream of the 3′ splice site and a free 3′ hydroxyl group on the 5′ exon. The resulting lariat RNA intermediate, with its slow migration in gels, is the most common assay for splicing in vitro. In the second step, attack of the 3′ hydroxyl on the phosphodiester bond at the 3′ splice site displaces the lariat intron with a 3′ hydroxyl group and results in joining of the two exons. The bimolecular nature of the intermediate in splicing indicated that the reaction must occur within a stable splicing body or spliceosome. Surprisingly, assembly and functioning of the spliceosome requires approximately 100 polypeptides and five small nuclear RNAs (snRNAs), not considering gene-specific RNA-binding factors. There are two distinct types of spliceosomes in most cells. The major class or U2-type spliceosome is universal in eukaryotes, whereas the minor class or U12-type spliceosome may not be present in some organisms. The evolutionary relationship of these two spliceosomes is uncertain. The sequence specificity for the splicing of introns must be encoded within the gene. In vertebrate genes, particularly for U2-type introns, the sequence specificity for splicing is not determined solely by the consensus sequences at the intron boundaries but is more broadly distributed within the gene. In contrast, the consensus sequences of the introns in the yeast Saccharomyces cerevisiae are generally adequate to specify...

550 citations

Journal ArticleDOI
01 Mar 1981-Cell

544 citations


Cited by
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Journal ArticleDOI
23 Jan 2004-Cell
TL;DR: Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.

32,946 citations

Journal ArticleDOI
Eric S. Lander1, Lauren Linton1, Bruce W. Birren1, Chad Nusbaum1  +245 moreInstitutions (29)
15 Feb 2001-Nature
TL;DR: The results of an international collaboration to produce and make freely available a draft sequence of the human genome are reported and an initial analysis is presented, describing some of the insights that can be gleaned from the sequence.
Abstract: The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.

22,269 citations

28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

Journal ArticleDOI
23 Jan 2009-Cell
TL;DR: The current understanding of miRNA target recognition in animals is outlined and the widespread impact of miRNAs on both the expression and evolution of protein-coding genes is discussed.

18,036 citations

Journal ArticleDOI
TL;DR: In this paper, a procedure for extracting plasmid DNA from bacterial cells is described, which is simple enough to permit the analysis by gel electrophoresis of 100 or more clones per day, yet yields DNA which is pure enough to be digestible by restriction enzymes.
Abstract: A procedure for extracting plasmid DNA from bacterial cells is described. The method is simple enough to permit the analysis by gel electrophoresis of 100 or more clones per day yet yields plasmid DNA which is pure enough to be digestible by restriction enzymes. The principle of the method is selective alkaline denaturation of high molecular weight chromosomal DNA while covalently closed circular DNA remains double-stranded. Adequate pH control is accomplished without using a pH meter. Upon neutralization, chromosomal DNA renatures to form an insoluble clot, leaving plasmid DNA in the supernatant. Large and small plasmid DNAs have been extracted by this method.

13,805 citations