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Doctoral thesis
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English

Analysis of in vivo RNA targets of human splicing factor SF1

Contributors

Antih, Nicolas

Directors

Kraemer, Angela

Defense date

2009-12-16

Abstract

The human splicing factor 1 (SF1) was originally isolated as a 75-kDa heat-stable protein required for presplicing complex formation. SF1 interacts with U2AF65, the large subunit of the U2 snRNP auxiliary factor, which is followed by the cooperative binding of the proteins to the branch point sequence (BPS), a conserved sequence of introns needed for the first transesterification reaction of splicing, and the polypyrimidine tract, respectively. Despite evidence from human and yeast splicing systems that SF1 is essential for early spliceosome assembly, further studies suggested that SF1 has a kinetic role in splicing and is only required for the splicing of introns with weak splice sites. Depletion of SF1 from human cell lines or yeast compromised viability and a knockout of sf1 in mice was lethal. Although no splicing defect was reported upon SF1 depletion in human cells or in yeast, the sf1 knockout mouse model demonstrated changes in the splicing pattern of several pre-mRNAs and an increased susceptibility to azoxymethane-induced colon tumorigenesis. In addition, other functions of SF1, in transcription regulation and pre-mRNA nuclear retention, were described.

Keywords

  • SF1
  • Alternative splicing
  • MiRNAs
  • U2AF65
  • U2AF35
  • Upf3a
  • NMD

UNIGE affiliation entities

Citation (ISO format)

ANTIH, Nicolas. Analysis of in vivo RNA targets of human splicing factor SF1. Doctoral Thesis, 2009. doi: 10.13097/archive-ouverte/unige:5149

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Technical informations

Creation

08/02/2010 11:43:00

First validation

08/02/2010 11:43:00

Update

14/03/2023 15:23:51

Status update

14/03/2023 15:23:51

Last indexation

13/05/2025 15:42:13
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