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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
21
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pubmed:dateCreated |
1992-8-26
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pubmed:abstractText |
Consensus sequences at the splice donor, splice acceptor, and lariat branch point regions are necessary but insufficient determinants of splice-site selection in nuclear precursor mRNAs. Sequences outside of these regions can have a significant effect on the utilization of splice sites. Although the mode of action of such sequences is undefined in most cases, higher order RNA structures have been suggested as a potential contributor to splice-site selection. During a detailed analysis of the splicing patterns of the human growth hormone transcript, we located 2 bases in the vicinity of the exon 3 major splice-acceptor site (B) which facilitate the utilization of a competing downstream acceptor (B'). The effects of a series of site-specific mutations on the splicing pattern demonstrate that these 2 bases function by stabilizing a specific stem-loop structure in the native transcript. This defined secondary structure selectively encompasses the upstream B splice-acceptor site together with its lariat branch point region. Increasing the predicted stability of this stem by point mutations results in a corresponding shift in splicing towards the alternative B' splice-acceptor site. These results indicate that a specific secondary structure within the native human growth hormone transcript controls the relative utilization of two competing splice-acceptor sites with the consequent generation of two functionally distinct hormone isoforms.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
|
pubmed:month |
Jul
|
pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
25
|
pubmed:volume |
267
|
pubmed:geneSymbol |
hGH-N,
hGH-V
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pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
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pubmed:pagination |
14902-8
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:1634529-Animals,
pubmed-meshheading:1634529-Base Sequence,
pubmed-meshheading:1634529-Cells, Cultured,
pubmed-meshheading:1634529-Growth Hormone,
pubmed-meshheading:1634529-Humans,
pubmed-meshheading:1634529-Mice,
pubmed-meshheading:1634529-Molecular Sequence Data,
pubmed-meshheading:1634529-Mutagenesis, Site-Directed,
pubmed-meshheading:1634529-Nucleic Acid Conformation,
pubmed-meshheading:1634529-Plasmids,
pubmed-meshheading:1634529-Polymerase Chain Reaction,
pubmed-meshheading:1634529-RNA Splicing,
pubmed-meshheading:1634529-Transcription, Genetic,
pubmed-meshheading:1634529-Tumor Cells, Cultured
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pubmed:year |
1992
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pubmed:articleTitle |
A native RNA secondary structure controls alternative splice-site selection and generates two human growth hormone isoforms.
|
pubmed:affiliation |
Howard Hughes Medical Institute, Department of Genetics, University of Pennsylvania, Philadelphia 19104.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|