The regulation of splicing of the human alpha sigma-tropomyosin pre-mRNA
The human alpha-s-tropomyosin pre-mRNA, encoded by the hTMnm gene, is alternatively spliced. In skeletal muscle cells, amino acids 189-213 are encoded by a skeletal-muscle specific exon, called SK. In all other cell types, amino acids 189-213 are encoded by an alternative exon called NM. The pattern...
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ndltd-bl.uk-oai-ethos.bl.uk-7376082019-03-05T15:46:07ZThe regulation of splicing of the human alpha sigma-tropomyosin pre-mRNATaylor, Claire Frances1996The human alpha-s-tropomyosin pre-mRNA, encoded by the hTMnm gene, is alternatively spliced. In skeletal muscle cells, amino acids 189-213 are encoded by a skeletal-muscle specific exon, called SK. In all other cell types, amino acids 189-213 are encoded by an alternative exon called NM. The pattern of splicing of SK and NM is mutually exclusive. Previous work had shown that in non-muscle cells, the selection of NM was determined by the intrinsic inactivity of the SK exon. SK inactivity was believed to be due to non-muscle-specific repression of the SK exon. The principal cis-acting sequence mediating this repression was believed to lie within the first fifteen nucleotides of the SK exon [Graham et al., 1992]. The aim of this thesis was to identify and characterise trans-acting factors which bound to the first fifteen nucleotides of the SK exon. It was hoped that this approach would identify the putative trans-acting repressor of the SK exon. Two factors which bound with apparent specificity were identified. The first of these was a 56 kDa protein, believed to be a member of the Y-box family of transcription factors. Irreproducibility of certain experiments, coupled with failure to successfully perform necessary confirmatory experiments mean that the status of p56 as a putative SK repressor remains uncertain. Data is presented to show that U1 snRNP also binds within the first fifteen nucleotides of SK, at a site which partially overlaps the 3' splice site. A hypothesis is proposed in which U1 snRNP is directly involved in the repression of SK in non-muscle cells. This finding is discussed in the context of related systems of alternative splicing.572University of Leicesterhttps://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.737608http://hdl.handle.net/2381/35167Electronic Thesis or Dissertation |
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572 Taylor, Claire Frances The regulation of splicing of the human alpha sigma-tropomyosin pre-mRNA |
description |
The human alpha-s-tropomyosin pre-mRNA, encoded by the hTMnm gene, is alternatively spliced. In skeletal muscle cells, amino acids 189-213 are encoded by a skeletal-muscle specific exon, called SK. In all other cell types, amino acids 189-213 are encoded by an alternative exon called NM. The pattern of splicing of SK and NM is mutually exclusive. Previous work had shown that in non-muscle cells, the selection of NM was determined by the intrinsic inactivity of the SK exon. SK inactivity was believed to be due to non-muscle-specific repression of the SK exon. The principal cis-acting sequence mediating this repression was believed to lie within the first fifteen nucleotides of the SK exon [Graham et al., 1992]. The aim of this thesis was to identify and characterise trans-acting factors which bound to the first fifteen nucleotides of the SK exon. It was hoped that this approach would identify the putative trans-acting repressor of the SK exon. Two factors which bound with apparent specificity were identified. The first of these was a 56 kDa protein, believed to be a member of the Y-box family of transcription factors. Irreproducibility of certain experiments, coupled with failure to successfully perform necessary confirmatory experiments mean that the status of p56 as a putative SK repressor remains uncertain. Data is presented to show that U1 snRNP also binds within the first fifteen nucleotides of SK, at a site which partially overlaps the 3' splice site. A hypothesis is proposed in which U1 snRNP is directly involved in the repression of SK in non-muscle cells. This finding is discussed in the context of related systems of alternative splicing. |
author |
Taylor, Claire Frances |
author_facet |
Taylor, Claire Frances |
author_sort |
Taylor, Claire Frances |
title |
The regulation of splicing of the human alpha sigma-tropomyosin pre-mRNA |
title_short |
The regulation of splicing of the human alpha sigma-tropomyosin pre-mRNA |
title_full |
The regulation of splicing of the human alpha sigma-tropomyosin pre-mRNA |
title_fullStr |
The regulation of splicing of the human alpha sigma-tropomyosin pre-mRNA |
title_full_unstemmed |
The regulation of splicing of the human alpha sigma-tropomyosin pre-mRNA |
title_sort |
regulation of splicing of the human alpha sigma-tropomyosin pre-mrna |
publisher |
University of Leicester |
publishDate |
1996 |
url |
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.737608 |
work_keys_str_mv |
AT taylorclairefrances theregulationofsplicingofthehumanalphasigmatropomyosinpremrna AT taylorclairefrances regulationofsplicingofthehumanalphasigmatropomyosinpremrna |
_version_ |
1718997193987194880 |