Functional Interactions in Transcription and Splicing of Ewing’s Sarcoma

Todorova, Roumiana

doi:10.5402/2013/184063

Cited by 1 publication

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“…A model of the functional interactions in transcription and splicing of Ewing's sarcoma is proposed in [ 86 ]. It is not clear at what stage the interacting partners are acting, their place in the process, and the mechanism of action.…”

Section: Resultsmentioning

confidence: 99%

Structure-Function Based Molecular Relationships in Ewing’s Sarcoma

Todorova

2015

BioMed Research International

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Ewing's Sarcoma Oncogene (ews) on chromosome 22q12 is encoding a ubiquitously expressed RNA-binding protein (EWS) with unknown function that is target of tumor-specific chromosomal translocations in Ewing's sarcoma family of tumors. A model of transcription complex was proposed in which the heterodimer Rpb4/7 binds to EAD, connecting it to Core RNA Pol II. The DNA-binding domain, provided by EFP, is bound to the promoter. Rpb4/7 binds RNA, stabilizing the transcription complex. The complex Rpb4/7 can stabilize the preinitiation complexes by converting the conformation of RNA Pol II. EWS may change its conformation, so that NTD becomes accessible. Two different mechanisms of interaction between EWS and RNA Pol II are proposed: (I) an intermolecular EWS-EWS interaction between two molecules, pushing conformation from “closed” to “open” state, or (II) an intramolecular interaction inside the molecule of EWS, pushing conformation of the molecule from “closed” to “open” state. The modified forms of EWS may interact with Pol II subunits hsRpb5 and hsRpb7. The EWS and EFPs binding partners are described schematically in a model, an attempt to link the transcription with the splicing. The proposed model helps to understand the functional molecular interactions in cancer, to find new partners and ways to treat cancer.

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Section: Resultsmentioning

confidence: 99%