This service will allow you to search for putative ESRs (exonic splicing regulatory elements) in your sequence

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285 ESR candidates [1] (Ast G. Lab)
238 ESEs [2] and 176 ESSs [4] (Burge CB. Lab)
2069 ESEs and 974 ESSs [3] (Chasin LA. Lab)
Additional RNA binding sites (Click here for their list)

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Abstract: Exonic-splicing regulatory (ESR) sequences are trans-acting factor binding sites that regulate constitutive and alternative splicing. on the combination of two features: (i) the evolutionary conservation of wobble positions between human and mouse orthologous exons (the wobble positions are almost free of coding constraints); and (ii) the analysis of the overabundance of sequence motifs, compared with their random expectation, given by their codon relative frequency. This method resulted in 285 significant ESR motifs.

Background: Splicing is the removal of introns and the joining of exons from mRNA precursors. The splicing reaction is catalyzed by the spliceosome - a complex which contains five snRNPs and at least 150 additional proteins. Four splice signals are known to be essential for accurate splicing: the 5' splice site (5'ss), the 3' splice site (3'ss), the polypyrimidine tract and the branch site sequence. These four splice signals alone cannot execute the splicing process correctly and it has been estimated that these splicing signals provide about one half of the information required for the recognition by the splicing machinery. This is exemplified by sequences containing motifs which agree with the consensus splice signals and yet are not being recognized by the splicing machinery. Thus, in addition to the information in the splice signals, cis-acting regulatory sequences in the pre-mRNA were shown to influencing splice sites choice by means of binding trans acting factors. These motifs are classified as exonic splicing enhancers (ESE) and silences (ESS). Alternative splicing is a process where more than one mRNA is produced from the same primary transcript or precursor messenger RNA by using different 5'ss and/or 3'ss, giving rise to functionally different proteins. ESEs and ESSs are required for the regulation of both constitutive and alternative splicing.

Proper citation should be given to the following publications:

  1. Goren A, Ram O, Amit M, Keren H, Lev-Maor G, Vig I, Pupko T and Ast G. Comparative analysis identifies exonic splicing regulatory sequences - the complex definition of enhancers and silencers. Mol cell. In press, 2006.
  2. Fairbrother WG, Yeh RF, Sharp PA, Burge CB. Predictive identification of exonic splicing enhancers in human genes. Science 2002;297:1007.1013. [PubMed] [Full Text]
  3. Zhang XH, Chasin LA. Computational definition of sequence motifs governing constitutive exon splicing.Genes Dev. 2004 Jun 1;18(11):1241-50. Epub 2004 May 14. [PubMed] [Full Text]
  4. Wang Z, Rolish ME, Yeo G, Tung V, Mawson M, Burge CB. (2004) Systematic identification and analysis of exonic splicing silencers. Cell 119: 831.845 [PubMed] [Full Text]

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