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Abiel Rindisbacher 28.05.2013 How to escape gene loss: new func?on or dosage benefit? •  Ancient gene duplica?on event in Saccharomyces cerevisiae •  Most duplicated genes got lost •  Some escaped (10%) → new func?on OR dosage benefit •  59 of 79 yeast ribosome genes encoded by 2 genes •  Previously thought to be func?onally redundant (dosage benefit) Wikipedia ASH1 •  Ash1 localises at the bud-­‐?p •  Needed for ASH1 mRNA localisa?on: Transla?on AND Transla?onal regula?on (repression) •  Some factors needed for localisa?on: → involved in ribosomal assembly (Loc1, Puf6) Effect of Loc1 on ASH1 mRNA localiza?on… …a consequence of its role in ribosomal assembly? → Loc1 regulates the transla?on of ASH1 mRNA not only localisa?on to the bud ?p Cells expressing the E3 reporter = ASH1 – Bud-­‐?p localisa?on → bud-­‐site posi?oning? Localisa?on of ASH1 mRNA in different mutants with random bud-­‐
site selec<on phenotype: Factors unrelated to transla?on → unique defects Factors related to transla?on → like in loc1Δ “Genes required for bud-­‐site selec<on are needed for the localiza?on of ASH1 mRNA” Func?onal specificity between duplicated ribosomal proteins? •  14/15 ribosomal proteins (RPs) implicated in bud-­‐site selec<on have duplicate •  Only one each needed for bud-­‐
site selec?on and ASH1 mRNA localisa?on •  “Transla?on of ASH1 mRNA requires a specific subset of duplicated RP paralogs” Data mining • Transcrip<onal profiles of cells lacking the RPs involved in ASH1 mRNA localiza?on → RP paralogs have specialized cellular roles beyond their effects on ASH1 • High-­‐throughput data (compiling phenotypic effects of absence of all non-­‐essen<al RP) → Duplicated RPs show different phenotypes from their paralogs ! No difference in expression level Paralog-­‐specific localiza?on? •  loc1Δ: Rpl7b and Rps18 → ER •  puf6Δ: Rpl7b → ER •  loc1Δpuf6Δ: o  Rps18b →ER o  Rpl7b → discrete cytoplasmic foci o  Rps18a → nucleolus → synthe?c defect “Paralogous RPs require different factors for their assembly and exhibit paralog-­‐
specific aberrant localiza<ons in the absence of certain factors” Are duplicated RPs playing dis?nct func?onal roles? •  Localized transla?on of ASH1 mRNA requires a specific subset of duplicated ribosomal protein genes •  Addi?onal levels of func<onal divergence between paralogs •  Func?onal specificity occurs in all duplicated ribosomal protein genes •  Paralog-­‐specific localiza?ons and assembly defects •  Not dosage effect → Yes Discussion Model: • ‘‘Loc1 is required for the assembly of ribosomes containing a specific subset of duplicated ribosomal proteins and this specialized ribosome is required for the regulated transla?on of ASH1 mRNA’’ • The model does not provide a mechanism • Specific ribosomes involved in other processes as well • There are indica?ons for specific ribosomes in other organisms as well Ribosome code Specific ribosomes: • Func?onally dis?nct RPs • Different forms of rRNA • Posiransla?onal modifica?ons → “Ribosome code”; similar to the “histone code” Transla?ng the Histone Code Thomas Jenuwein and C. David Allis Ø New level of complexity in the regula<on of gene expression Thank you for your aien?on!