Knowledge Exchange – Things Common in Yeast and Humans

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In our Genome Browser we can see both exons, introns and UTRs all the time – they are represented as lines in a sequence of letters ACTAGACTA…. In real molecules they are not linear, but are arranged into a peculiar 3D structure. Later, genes transcribed to this pre-messenger RNAs are cut into pieces and glued back again in a process we know as splicing.

Splicing is prevalent in MHC / HLA genes also, we just started to understand how the its machinery works, what are the steps in exon definition, and the role of enhancer and silencer motifs. Looking at the 3D structure of the yeast spliceosome we can see the difficulties structural chemists are facing: the RNA conformation is complex, unstable and difficult to crystallize. Nevertheless, it gives insights about the conformation changes you can have during splicing steps.

Also, to understand aromatic stacking and the role of non-Watson-Crick base pairs, it is good to practice your eyes in one of the largest RNA structure solved so far: the bacterial ribosome. In the pictures you can see some of us are really into the stacking of pactamycin (PDB structure 1HNX).

4pkd_1-2

4PKD: stacking between amino acids and nucleic acids

4pjo_1-2

4PJO: the Zn-finger nucleic acid recognition part in U1 snRNP

3jb9_1-2

3JB9: the catalytic core of the yeast spliceosome: non-Watson-Crick base pairs are doing the job

1hnx_1-2

1HNX: pactamycin bound to bacterial ribosome: a test case to look at H-bonds and aromatic stacking

 – By Szilveszter Juhos