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ISMB2010:
ISMB
Keynote: Steven Brenner - Ultraconserved nonsense: gene regulation by splicing & RNA surveillance
July 11, 2010
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Barb Bryant, Mickey Kosloff, Deepak Singh and 4 other people liked this
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
Related reference: http://compbio.berkeley.edu/people...
- Shannon McWeeney
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
question of why conserved - not protein coding, no obvious significant RNA secondary structure
- Shannon McWeeney
No proteins are produced from these genes.
- Roland Krause
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