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ISMB
Keynote: Steven Brenner - Ultraconserved nonsense: gene regulation by splicing & RNA surveillance
ISMB2010 just kicked off - Venkata P. Satagopam
Prof Søren Brunak introducing Steven Brenner, ISCB overton prize winner - Venkata P. Satagopam
Brenner contributed to many fields in bioinformations, starting in structureal biology ober RNA to metagenomics. - Roland Krause
A short biography, summarizing Soren Brunaks kind introduction http://compbio.berkeley.edu/people... - Roland Krause
The morphology of steves paper: http://www.improbable.com/airchiv... - Shannon McWeeney
Intro: The ultraconservative (as seen from Berkely) and nonsense (as found in Through the Looking Glass - Roland Krause
The jabberwocky poem does have meanings and is elegantly crafted. - Roland Krause
Generally, nonsens in biology is bad. - Roland Krause
Nonsense is generally bad, even in a codon - Venkata P. Satagopam
Truncated proteins might interfere with physiological function (dominant negative). The cell removes such transcripts through nonsense-mediated decay (NMD). - Roland Krause
Good example for NMD: Sox10 - Roland Krause
Mutations early in the gene leads to less severe phenotypes than later ones - Roland Krause
NMD is an mRNA surveillance system - Venkata P. Satagopam
NMD important to development of the immunesystem and cleans up other transcriptional errors. - Roland Krause
We do not know how NMD works outside the mammals. - Roland Krause
The mechanism involves the splicing machinery. If a stop is found wwithin 50nt upstream of the exon junction complex, it is removed.. - Roland Krause
50 nucleotide rule - translated normally or degraded by NMD - Venkata P. Satagopam
brilliant nytimes article title - surviving on low number of genes - Shannon McWeeney
splicing can introduce PTC - premature termination codon - Venkata P. Satagopam
AS as mechanism to introduce PTCs - can lead to unproductive splicing - Shannon McWeeney
these isoforms often have PTC - Venkata P. Satagopam
Humans have fewer genes but better genes, due to AS. - John Greene from fftogo
Are PTC splice forms funcitonal? - Venkata P. Satagopam
Many PTC mRNAs are noise - Venkata P. Satagopam
analgous mechanism to shrinter: http://www.geeky-gadgets.com/cool-ga... - Shannon McWeeney
Humans have fewer genes but better genes, due to AS. - John Greene from fftogo
Alt splicing can yield isoforms differentially subjected to NMD - Venkata P. Satagopam
SR protein - 11 in human which are serine and arginine rich - Venkata P. Satagopam
SR proteins have premature stop codons. - Roland Krause
SR genes has mRNAs with premature termination codons - Venkata P. Satagopam
AS of PTC isoforms is mechanism for autoregulation of proteins - Ted Laderas
NMD has a large effect on isoform abundance - Venkata P. Satagopam
NMD has impact on isoform abundance - example of NMD clearing the major isoform - Shannon McWeeney
minor isoforms are only shared 25% of time - modrek and lee 2003 - Shannon McWeeney
Not just anecdotal stories, splice patterns are conserved in mouse, implying functional significance. - Roland Krause
(Unpulbished work) - Roland Krause
All the SR proteins are talking to each other - Venkata P. Satagopam
SR proteins 'compensate' for each other via coupling via AS and NMD - Ted Laderas
SR genes have ultraconversed elements .. Bejerano et al 2004 Science 304: 1321 - Venkata P. Satagopam
Most ultraconserved regions are in intergenic regions, the regions in SR within genes. - Roland Krause
No proteins are produced from these genes. - Roland Krause
question of why conserved - not protein coding, no obvious significant RNA secondary structure - Shannon McWeeney
The reason why SR sequences are highly conserved - most of the seq are not protein coding, - Venkata P. Satagopam
no repetitive elements - Venkata P. Satagopam
why conserved part 2 - no overrepresentation of binding / regulatory elements - Shannon McWeeney
No simple explanations e.g. from miRNA binding etc. - Roland Krause
no similarity elsewhere in genome except retropseudogenes - Venkata P. Satagopam
analysis on origin of unproductive splicing - Shannon McWeeney
No sequence similarity between the conserved elements. Seems to have been introduced mutliple times. - Roland Krause
mouse and human SRp55 conserved but changing - Venkata P. Satagopam
working on chordate SR proteins - Venkata P. Satagopam
here intron and exon structure is more informative - Venkata P. Satagopam
at this point - he has requested no further blogging - unpublished work - Shannon McWeeney
no blog slides may be over - Burkhard Rost
# Looks like interesting work. - Roland Krause
wonderful talk - Shannon McWeeney
Tells a (hard to blog) story about the successful treatment of collaborator with novel treatment based on genotyping. - Roland Krause
Wow - what a conclusion! Fantatic talk... - John Greene from fftogo
# Certainly great work. The talk was nice too, and he only bitched at other reseachers in person once, another step up. - Roland Krause
"Ultraconversed elements in SR genes ONLY show similarity to retropseudogenes" - what does this mean? Any takers? - Saravanamuttu Gnaneshan