Detailed mapping of the sites of interaction of polypyrimidine tract binding protein with its RNA targets: viral and cellular IRESs and pre-mRNAs.

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The strong physical, behavioural, and mental similarity of identical twins shows that it is our genetic material that largely specifies what we are. This genetic material is our DNA, which can be regarded as an exceedingly long 'tape' (e.g. an enormous video tape) with some 3 billion bits of information, coding for the numerous different types of protein which carry out most of our bodily functions. The DNA can be thought of as the 'master tape', an archive of thousands of normal length videos joined together. The process of decoding this information in the DNA involves first making a working copy of one of these videotapes in the archive. In fact the information in this initial copy is segmented, with the meaningful segments interspersed with meaningless sections. Consequently, the meaningful segments in this initial copy need to be cut out and spliced together, much as cine films were created by splicing in the pre-electronic era. In many cases, this splicing can occur in slightly different ways, with some meaningful segments excluded in some cells or some circumstances, but included in other cells/circumstances. Thus the initial copy of the archived 'video' can give rise to more than one variant of the final playable video. A protein known as polypyrimidine tract binding protein (PTB) exerts a strong influence on the alternative splicing, causing the inclusion of some meaningful segments and the exclusion of others. After the video has been spliced together it is decoded by a small particle known as a ribosome, which essentially carries out an analogous function to that of a video recorder (VCR) as it decodes the information as pictures. The 'biological videos' are similar to real videos in so far as the part of the tape with the pictorial information is preceded by a short leader length that has no information. In most cases our biological VCR (the ribosome) finds the point where the true information starts by searching or scanning in fast-forward mode through the whole meaningless leader. However, with some such videos the biological VCR is able to go straight to the starting point where the meaningful pictorial information begins without searching through the meaningless leader section, and in many such cases PTB is necessary for the direct location of the start position by the biological VCR. The aim of this project is to find out how PTB (a) causes the biological VCR to locate these starting sites without a need for searching through the tape from the very start, and (b) can influence the exact pattern in which the different meaningful segments are spliced together to give the finished video tape.