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  1. TI=Splicing of many human genes involves sites embedded within introns
  2. AU="Zicheng Zeng"

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  1. Artikel ; Online: Splicing of many human genes involves sites embedded within introns.

    Kelly, Steven / Georgomanolis, Theodore / Zirkel, Anne / Diermeier, Sarah / O'Reilly, Dawn / Murphy, Shona / Längst, Gernot / Cook, Peter R / Papantonis, Argyris

    Nucleic acids research

    2015  Band 43, Heft 9, Seite(n) 4721–4732

    Abstract: The conventional model for splicing involves excision of each intron in one piece; we demonstrate ... this inaccurately describes splicing in many human genes. First, after switching on transcription of SAMD4A, a gene ... genes yield products generated by such intermediate intron splicing. These products are present at ∼15 ...

    Abstract The conventional model for splicing involves excision of each intron in one piece; we demonstrate this inaccurately describes splicing in many human genes. First, after switching on transcription of SAMD4A, a gene with a 134 kb-long first intron, splicing joins the 3' end of exon 1 to successive points within intron 1 well before the acceptor site at exon 2 is made. Second, genome-wide analysis shows that >60% of active genes yield products generated by such intermediate intron splicing. These products are present at ∼15% the levels of primary transcripts, are encoded by conserved sequences similar to those found at canonical acceptors, and marked by distinctive structural and epigenetic features. Finally, using targeted genome editing, we demonstrate that inhibiting the formation of these splicing intermediates affects efficient exon-exon splicing. These findings greatly expand the functional and regulatory complexity of the human transcriptome.
    Mesh-Begriff(e) Cells, Cultured ; Exons ; Human Umbilical Vein Endothelial Cells/metabolism ; Humans ; Introns ; RNA Splice Sites ; RNA Splicing ; Repressor Proteins/genetics ; Transcription, Genetic
    Chemische Substanzen RNA Splice Sites ; Repressor Proteins ; SAMD4A protein, human
    Sprache Englisch
    Erscheinungsdatum 2015-04-20
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 186809-3
    ISSN 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
    ISSN (online) 1362-4962 ; 1362-4954
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gkv386
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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    Verfügbar in ZB MED Köln/Königswinter

    Zs.A 1067: Hefte anzeigen Standort:
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  2. Artikel: An intron enhancer recognized by splicing factors activates polyadenylation.

    Lou, H / Gagel, R F / Berget, S M

    Genes & development

    1996  Band 10, Heft 2, Seite(n) 208–219

    Abstract: ... CT/CGRP) involves alternative inclusion of a 3'-terminal exon (exon 4) embedded within a six exon ... enhancement via interaction with factors normally associated with functional 5' splice sites. Mutation ... distributed. Inclusion of exon 4 requires an enhancer sequence located within the intron downstream ...

    Abstract Alternative processing of the pre-messenger RNA encoding calcitonin/calcitonin gene-related peptide (CT/CGRP) involves alternative inclusion of a 3'-terminal exon (exon 4) embedded within a six exon primary transcript. Expression of CT/CGRP in transgenic mice indicates that inclusion of exon 4 occurs in a wide variety of tissues, suggesting that the factors responsible for exon 4 inclusion are widely distributed. Inclusion of exon 4 requires an enhancer sequence located within the intron downstream of the poly(A) site of exon 4. Here we show that the intron enhancer activated in vitro polyadenylation cleavage of precursor RNAs containing the CT/CGRP exon 4 poly(A) site or heterologous poly(A) sites. To our knowledge this is the first example of an intron-located enhancer that facilitates polyadenylation. Within the enhancer sequence is a 5' splice site sequence immediately preceded by a pyrimidine tract. This 5' splice site sequence was required for enhanced polyadenylation and was recognized by both U1 small nuclear ribonucleoproteins (snRNPs) and alternative splicing factor/splicing factor 2 (ASF/SF2). Enhancement of polyadenylation required U1 RNA, suggesting that the 5' splice site sequence within the enhancer mediates enhancement via interaction with factors normally associated with functional 5' splice sites. Mutation of the polypyrimidine track of the enhancer also inhibited in vitro polyadenylation cleavage. Oligonucleotide competitions and UV cross-linking indicated that the enhancer pyrimidine track binds the polypyrimidine tract binding protein (PTB), but not U2 snRNP auxiliary factor (U2AF), and that binding of PTB was required for maximal enhancer-mediated polyadenylation. These results suggest that the enhancer binds known splicing factors, and that binding of these factors activates polyadenylation cleavage. Furthermore, these results suggest that regulation of alternative processing of CT/CGRP could occur at the level of polyadenylation, rather than splicing.
    Mesh-Begriff(e) Alternative Splicing ; Animals ; Base Sequence ; Binding Sites ; Calcitonin/genetics ; Calcitonin Gene-Related Peptide/genetics ; DNA-Binding Proteins/metabolism ; Enhancer Elements, Genetic ; Exons ; HeLa Cells ; Humans ; Introns ; Mice ; Molecular Sequence Data ; Nuclear Proteins/metabolism ; Poly A/metabolism ; Polypyrimidine Tract-Binding Protein ; RNA Precursors/metabolism ; RNA-Binding Proteins/metabolism ; Ribonucleoprotein, U1 Small Nuclear/metabolism ; Serine-Arginine Splicing Factors ; mRNA Cleavage and Polyadenylation Factors
    Chemische Substanzen DNA-Binding Proteins ; Nuclear Proteins ; RNA Precursors ; RNA-Binding Proteins ; Ribonucleoprotein, U1 Small Nuclear ; mRNA Cleavage and Polyadenylation Factors ; Polypyrimidine Tract-Binding Protein (139076-35-0) ; Serine-Arginine Splicing Factors (170974-22-8) ; Poly A (24937-83-5) ; Calcitonin (9007-12-9) ; Calcitonin Gene-Related Peptide (JHB2QIZ69Z)
    Sprache Englisch
    Erscheinungsdatum 1996-01-15
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 806684-x
    ISSN 1549-5477 ; 0890-9369
    ISSN (online) 1549-5477
    ISSN 0890-9369
    DOI 10.1101/gad.10.2.208
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 2292: Hefte anzeigen Standort:
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    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
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