"Molecular characterisation of leader sequences which

can also mediate ribosome 'skipping' "

Staff:...Dr. Andriy Sukhodub..&...Dr. Garry Luke

1/4/2010 - 31/3/2013: £509,670.


Backgound: The '2A' region of foot-and-mouth disease virus is only 18aa long, but we have shown this oligopeptide specifies a newly-discovered translational effect: ribosome 'skipping' . Simple inspection of databases indicated that similar sequences were present in the genomes of other, closely related, picornaviruses and we showed that these sequences also mediated this 'skipping' effect. Analyses of databases showed that '2A-like' sequences were also present in the genomes of other viruses not related to picornaviruses. Indeed, such sequences are now know to be present (and active) in many viruses. We also detected 2As in the genomes of the pathogens Trypanosome cruzi and T. brucei, vivax, congolense etc. These 2As were detected in the N-terminal regions of the single, long, ORF of these non-LTR retrotansposons. We have very recently discovered 2As in the genomes of many other metazoan organisms. These 2As are also found in non-LTR retrotansposons but, importantly, in many other cellular genes. In very many cases these 2Aa are present at the N-terminus of the ORF (encoded by their own mini-exons) and, in some cases, we have shown that these 2As also posses signal sequence activity.

The Project funded by the BBSRC is to perform further molecular biological characterisation of these sequences - a classical structure/function analysis - but, importantly, to further develop these sequences for novel biotechnological and biomedical applications.


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