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A new model argues against Just in time synthesis in M phase

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!. C lassic thinking !.

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A new model argues against Just in time synthesis in M phase

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  1. A new model arguesagainstJust in time synthesisin M phase Bjørn Sponberg Supervisor: Erik L. L. Sonnhammer Department of Biochemistry and Biophysics

  2. The eukaryoticcell cycle Just in time synthesis In all phases! Classicthinking!

  3. Current view: Just in time synthesis Problem withtranscription in M phase! Regulatorylevel 1: DNA level Regulatorylevel 2. Nucleosomelevel Regulatorylevel 3. 3D level

  4. Hypothesis: Extremeevolutionarypressure on cell cycle speed. Conclusion: the first unicellulareukaryotic cells wereforced to find the fastest division mechanism that was available to them.

  5. P-body vesiclescan store and releasetranscripts. P-bodies can increase cell cycle speed Movetranscription from M phase to G1 phase

  6. The new model callthem: P-body transcripts To regulate their uniqueexpressionroute, P-body transcriptsshould have uniquesequence features.

  7. INTRON 5’UTR 3’UTR CDS P-Bodytranscripts DETECT DIFFERENCES WITH: SVM & BLAST Normal transcripts

  8. METHODS ”The wheel”

  9. BLAST SVM ”The wheel” 460 GENES DOWNLOADED G2M M 270° 225° 315° 360°, 0° 180° 22.5° 135° 45° 45° S G1 67.5° 90° • TOOLS: • Support VectorMachine (SVM) • RedvsBlueKmerlengths 7 nucleotides • Data classificationbased on sequence features (kmer’s) in the red and bluedatasets. • Value: Matthews correlationcoefficient (MCC) • BLAST • Red Wordsize 7 • Sequencealignments of all combinations in the red dataset. • Value: ScoreBit (sequencesimilarity score) 16 positions (22.5°*16 = 360°) SCORE Two plots: SVM: CMassification score (MCC accuracy) BLAST: Sequencesimilarity score (ScoreBit) 360°

  10. BLAST SVM Expected plot G2M M P-body transcripts G2 M 0° 180° Normal transcripts S G1 S G1 Score 45° 225° BLAST 90° 180° 135° SVM Wheel position° 0° 360°

  11. Results

  12. BLAST SVM M G2M 225° 315° 0° As hypothesized 135° 45° 45° S 67.5° G1

  13. BLAST SVM M G2M HOMOLOGY! 270° 225° 315° 0° 180° 45° 135° S G1 90°

  14. BLAST SVM M G2M 270° 225° 315° 0° 180° As hypothesized 45° 135° S G1 90° SURPRISE! • Minorsplicesome system! • Active in M phase! • Maybe it is part of the P-body genes?

  15. BLAST SVM Not as hypothesized! M G2M 270° 225° 315° So far: 5’UTR and intron have 0° 180° Not as hypothesized! 45° 135° S G1 90°

  16. 1) 5.73 longer averagelength in 3’UTR 2) Affectshomology/regulatory signal G2M M As hypothesized! HOMOLOGY 0° REGULATORY 67.5° S G1 Homology! As hypothesized! As hypothesized!

  17. Summary Not as hypothesized (Homology) As hypothesized (P-body transccripts) As hypothesized (P-body transccripts) As hypothesized (P-body transccripts)

  18. SVM BLAST UTRscan UTRscanSearching for 46annotated 3’UTR and 5’UTR regulators G2M M BOTH REGULATORS ARE INVOLVED IN TEMPORAL TRANSLATION CONTROL! 0° 180° S G1

  19. 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 transcriptsare 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.

  20. 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. • CharlesworthA, Wilczynska A, Thampi P, Cox LL, MacNicol AM. Musashi regulates the temporal order of mRNA translation during Xenopusoocyte maturation. EMBO J. 2006 Jun 21;25(12):2792-801.

  21. Acknowledgement Supervisor: Erik L. L. Sonnhammer

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