a new model argues against just in time synthesis in m phase bjørn sponberg supervisor: erik l. l....
TRANSCRIPT
A new model argues against Just in time synthesis in M phase
Bjørn Sponberg
Supervisor: Erik L. L. Sonnhammer
Department of Biochemistry and Biophysics
The eukaryotic cell cycle
Just in time synthesis
In all phases!
Classic thinking!
Current view: Just in time synthesis
Problem with transcription in M phase!
Regulatory level 1: DNA level Regulatory level 2. Nucleosome levelRegulatory level 3. 3D level
Hypothesis : Extreme evolutionary pressure on cell cycle speed.
Conclusion: the first unicellular eukaryotic cells were forced to find the fastest division mechanism that was available to them.
P-body vesicles can store and release transcripts.
P-bodies can increase cell cycle speed
Move transcription from M phase to G1 phase
The new model call them: P-body transcripts
To regulate their unique expression route, P-body transcripts should have unique sequence features.
DETECT DIFFERENCES WITH: SVM & BLAST
5’UTR 3’UTRCDS
INTRON
P-Body transcripts
Normal transcripts
METHODS”The wheel”
”The wheel”
M G2M
360°, 0°
22.5°
135°90°
180°
225°270°
315°
G1S
SCORE
67.5°45°
TOOLS:•Support Vector Machine (SVM)Red vs Blue Kmer lengths 7 nucleotidesData classification based on sequence features (kmer’s) in the red and blue datasets.Value: Matthews correlation coefficient (MCC)•BLAST Red Wordsize 7Sequence alignments of all combinations in the red dataset.Value: ScoreBit (sequence similarity score)
460 GENES DOWNLOADED
SVMBLAST
Two plots:SVM: CMassification score (MCC accuracy)BLAST: Sequence similarity score (ScoreBit)
360°
16 positions (22.5°*16 = 360°)
45°
Expected plot
45°90°
135°180°
0° 360°
225°
SVM
BLAST
M G2 0°180°
G1S
Wheel position °
Score
P-body transcripts
Normal transcripts
G2M M
G1S
SVMBLAST
Results
0°
45°135°
225° 315°
67.5°
M
G1S
G2M
SVMBLAST
45°
As hypothesized
M G2M
0°
45°135°90°
180°
225°270°
315°
G1S
SVMBLAST
HOMOLOGY!
M G2M
0°
45°135°90°
180°
225°270°
315°
G1S
•Minor splicesome system!• Active in M phase!• Maybe it is part of the P-body genes?
SVMBLAST
As hypothesized
SURPRISE!
M G2M
0°
45°135°90°
180°
225°270°
315°
G1S
SVMBLAST
So far: 5’UTR and intron have
Not as hypothesized!
Not as hypothesized!
1) 5.73 longer average length in 3’UTR 2) Affects homology/regulatory signal
M G2M
G1S 67.5 °
0 ° HOMOLOGY
REGULATORY
As hypothesized!
As hypothesized!
As hypothesized!Homology!
Summary
As hypothesized(P-body transccripts)
Not as hypothesized (Homology)
As hypothesized(P-body transccripts)
As hypothesized(P-body transccripts)
UTRscan Searching for 46 annotated 3’UTR and 5’UTR regulators
0°180°
G2M M
G1S
SVMBLAST
UTRscan
BOTH REGULATORS ARE INVOLVED IN TEMPORAL TRANSLATION CONTROL!
CONCLUSION
• We have found the possible existence of the hypothesized P-body genes and their localization - as predicted in the new model.
• If so, the P-body transcripts are probably temporally regulated via three gene regions; three prime untranslated region (3'UTR), five prime untranslated region (5'UTR) and introns.
• Musashi binding element (MBE) and Upstream Open Reading Frame (uORF) are potential regulatory candidates in the P-body transcripts 3’UTR and 5’UTR.
References• http://
www.sparknotes.com/biology/cellreproduction/cellcycle/section2.rhtml• de Lichtenberg U, Jensen LJ, Brunak S, Bork P. Dynamic complex formation
during the yeast cell cycle. Science. 2005 Feb 4;307(5710):724-7.• Rokas A. The origins of multicellularity and the early history of the genetic
toolkit for animal development. Annu Rev Genet. 2008;42:235-51.• Parker R, Sheth U. P bodies and the control of mRNA translation and
degradation. Mol Cell. 2007 Mar 9;25(5):635-46.• David P. Mindell Axel Meyer. Homology evolving Volume 16, Issue 8, 1
August 2001, Pages 434–440.• Charlesworth A, Wilczynska A, Thampi P, Cox LL, MacNicol AM. Musashi
regulates the temporal order of mRNA translation during Xenopus oocyte maturation. EMBO J. 2006 Jun 21;25(12):2792-801.
Acknowledgement
Supervisor: Erik L. L. Sonnhammer