magista fg Protein splicing upsets the DNA colinearity paradigm

Protein splicing upsets the DNA colinearity paradigm

Black hypervenom novel mechanism of protein processing found

September 8, Brussels and New York Understanding medical research problems often relies on the direct, linear relationship between the sequence of a protein and the DNA encoding that protein. In fact, colinearity of DNA and protein sequences is thought to be a fundamental feature of the universal genetic code. However, a paper published today in Science by a team from the Brussels Branch of the global Ludwig Institute for Cancer Research (LICR) and the Seattlebased Fred Hutchinson Cancer Research Center (FHCRC), shows that a protein can be rearranged so that it is no longer colinear with its encoding DNA.

Genes have stretches of (protein) coding DNA sequences interspersed with stretches of noncoding DNA sequences. The first step in making the protein is the faithful transcription of the entire gene’s sequence into an RNA sequence. The RNA is then magista fg ‘spliced’ such that the noncoding sequences are removed and the coding sequences are assembled in a black hypervenom linear fashion to form the template for translation from RNA to protein.

“Until now it was thought that colinearity of DNA and protein sequences was only interrupted by RNA splicing, says LICR’s Dr. “This new study shows that protein splicing also occurs, and may even result in protein fragments, or peptides, being spliced together in the order opposite to that which occurs in the parental protein,

According to Dr. Van den Eynde, this novel phenomenon occurs during the physiological function of ‘antigen processing,’ which produces antigenic peptides; the ‘red flags’ that mark cells for destruction by the immune system.

The immune system attacks ‘foreign’ cells be they tumor cells, virally infected, or donated by another person when T lymphocytes recognize antigenic peptides displayed on the cell surface. The antigens are created by ‘proteasomes,’ components of magista fg the cell machinery that cut foreign proteins into peptides that are then displayed on the cell surface for recognition and destruction by CD8+ T lymphocytes. However, the Belgium/USA team has found that proteasomes can also splice the peptide fragments together in a reverse order to that encoded by the protein’s DNA black hypervenom sequence template. This takes the possible number of black hypervenom antigens from any one protein into potentially thousands of sequence configurations.

The sequence of the first human cancerspecific antigen, which was identified at the LICR Brussels Branch, has allowed the development of antigenspecific cancer vaccines that are in clinical trials around the world. This study describes a mechanism that significantly extends the number of antigenic peptides that can be produced from a single protein, and therefore widens the applicability of peptide vaccines against cancer and infectious diseases black hypervenom.