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Patrick Cormier/ Robert Bellé Adrien Richard Ouverture BioTempo TÂCHE 5 : Applications 2. Initiation dans le modèle oursin a: courte présentation de l’Unité b: traduction & oursin c: vers un réseau traductionnel

Ouverture BioTempo TÂCHE 5 : Applications a: courte ...biotempo.genouest.org/data/KickOffCormier2.pdf · Sphaerechinus granularis But what about the translational machinery involved

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Page 1: Ouverture BioTempo TÂCHE 5 : Applications a: courte ...biotempo.genouest.org/data/KickOffCormier2.pdf · Sphaerechinus granularis But what about the translational machinery involved

Patrick Cormier/ Robert BelléAdrien Richard

Ouverture BioTempoTÂCHE 5 : Applications

2. Initiation dans le modèle oursin

a: courte présentation de l’Unitéb: traduction & oursinc: vers un réseau traductionnel

Page 2: Ouverture BioTempo TÂCHE 5 : Applications a: courte ...biotempo.genouest.org/data/KickOffCormier2.pdf · Sphaerechinus granularis But what about the translational machinery involved

Translation

Cell cycle

Development

P. Cormier

Erythrocyte

Cellular

Physiology

S. Egée

Vertebrates

Development

Evolution

S.Mazan

Retinoic

acid

Development

Evolution

M. Schubert

Mer

&SantéMer

&Santé

-Origine et scénario évolutif des mécanismes impliqués Evo Devo & Biologie systémique

-Etudes des principes fondamentaux qui président à la vie de la cellule et au développement de modèles marins (deutérostomiens) :

-Recherche translationnelle

UMR 7150

Direction Patrick CormierDir. Patrick Cormier

Page 3: Ouverture BioTempo TÂCHE 5 : Applications a: courte ...biotempo.genouest.org/data/KickOffCormier2.pdf · Sphaerechinus granularis But what about the translational machinery involved

Mer

&SantéMer

&Santé

Scénario évolutif

Biologie systémique

(collab. Siegel A, PEPS

& ANR )

Activité traductionnelle en

Condition physiologique

Mol Rep. Dev., 2010

Traduction cap-dépendante

Transfert

Brevet déposé

Structures

Régulation traductionelle

Science, 2006PloS One 2009, Dev Biol, 2011

Nuc Aci Res., 2010

Mol Rep. Dev., 2010

Équipe TCCD

Page 4: Ouverture BioTempo TÂCHE 5 : Applications a: courte ...biotempo.genouest.org/data/KickOffCormier2.pdf · Sphaerechinus granularis But what about the translational machinery involved

mRNA

mRNA

Global

protein

synthesis

translational regulation

mRNA

protein

protein

protein

stimulation

A mRNA is not systematically translated

a: courte présentation de l’Unitéb: traduction & oursinc: vers un réseau traductionnel

Page 5: Ouverture BioTempo TÂCHE 5 : Applications a: courte ...biotempo.genouest.org/data/KickOffCormier2.pdf · Sphaerechinus granularis But what about the translational machinery involved

A mRNA is not systematically translated

mRNA

mRNA

Global

protein

synthesis

translational regulation

mRNA

protein

stimulation

Specific

protein

synthesis

Page 6: Ouverture BioTempo TÂCHE 5 : Applications a: courte ...biotempo.genouest.org/data/KickOffCormier2.pdf · Sphaerechinus granularis But what about the translational machinery involved

Cap

bindingpartner

Cis

Non coding RNA

cis-acting factor

trans-acting factor

Old players, new concepts

microRNA for macro function

Gene Regulatory Network

Temporal precision and substrate specificity

Page 7: Ouverture BioTempo TÂCHE 5 : Applications a: courte ...biotempo.genouest.org/data/KickOffCormier2.pdf · Sphaerechinus granularis But what about the translational machinery involved

G1 MM 2 2 cellscellsS

sea urchin early development as a model for translation and cell cycle analysis

Sphaerechinus granularis

Global protein synthesis increases

Page 8: Ouverture BioTempo TÂCHE 5 : Applications a: courte ...biotempo.genouest.org/data/KickOffCormier2.pdf · Sphaerechinus granularis But what about the translational machinery involved

G1G1 metaphasemetaphase 2 2 cellscells

MPF activity

S

first mitotic division in sea urchin

CDK1

Nobel price 2001 (Hartwell, Nurse and Hunt)

Page 9: Ouverture BioTempo TÂCHE 5 : Applications a: courte ...biotempo.genouest.org/data/KickOffCormier2.pdf · Sphaerechinus granularis But what about the translational machinery involved

Global protein synthesis increases

G1 MM 2 2 cellscellsS

sea urchin early development as a model for translation and cell cycle analysis

Protein synthesis inhibitor

Post-transcriptional processesTranslational and post-translational processes

Sphaerechinus granularis

But what about the translational machinery involved ?

Page 10: Ouverture BioTempo TÂCHE 5 : Applications a: courte ...biotempo.genouest.org/data/KickOffCormier2.pdf · Sphaerechinus granularis But what about the translational machinery involved

Translation can be regulated at different levels

Page 11: Ouverture BioTempo TÂCHE 5 : Applications a: courte ...biotempo.genouest.org/data/KickOffCormier2.pdf · Sphaerechinus granularis But what about the translational machinery involved

Translation initiation

From Sonenberg and Hinnebush, Cell 2009

Page 12: Ouverture BioTempo TÂCHE 5 : Applications a: courte ...biotempo.genouest.org/data/KickOffCormier2.pdf · Sphaerechinus granularis But what about the translational machinery involved

fertilization

4EBP

4G

Global protein synthesis off

FRAP/mTOR

A summary from

Cormier et al., 2001, Dev Biol

Salaün et al., 2003, Dev Biol

Salaün et al., 2004,Exp. Cell Res.

Salaün et al., 2005, J. cell Science

Oulhen et al., 2007, J. cell Science

Sea urchin unfertilized egg

Page 13: Ouverture BioTempo TÂCHE 5 : Applications a: courte ...biotempo.genouest.org/data/KickOffCormier2.pdf · Sphaerechinus granularis But what about the translational machinery involved

fertilization

4E

4G

4G

Global protein synthesis on

15 minutes post-fertilization

A summary from

Cormier et al., 2001, Dev Biol

Salaün et al., 2003, Dev Biol

Salaün et al., 2004,Exp. Cell Res.

Salaün et al., 2005, J. cell Science

Oulhen et al., 2007, J. cell Science

Page 14: Ouverture BioTempo TÂCHE 5 : Applications a: courte ...biotempo.genouest.org/data/KickOffCormier2.pdf · Sphaerechinus granularis But what about the translational machinery involved

mRNA

mRNA

Global

protein

synthesis

translational regulation

Cyclin B mRNA

protein

Cyclin B protein

protein

fertilization

20-30 minutes

Post-fertilization

A summary from

Cormier et al., 2001, Dev Biol

Salaün et al., 2003, Dev Biol

Salaün et al., 2004,Exp. Cell Res.

Salaün et al., 2005, J. cell Science

Oulhen et al., 2007, J. cell Science

Page 15: Ouverture BioTempo TÂCHE 5 : Applications a: courte ...biotempo.genouest.org/data/KickOffCormier2.pdf · Sphaerechinus granularis But what about the translational machinery involved

Translation factors genes in S. purpuratus genome

Name other

name

SPU # function tiling expression

data Initiation

eIF1 016208 AUG recognition +++

eIF1A 026084 +

eIF2alpha

eIF2beta

eIF2gamma

003646

009150

020412

binds GTP, Met-tRNA; GTPase ++

++

++

eIF2Balpha

eIF2Bbeta

eIF2Bgamma

eIF2Bdelta

eIF2Bepsilon

021689

004173

005651

010743

015443

GTP exchange activity on eIF2 ++

+++

+

+

++

eIF3a

eIF3b

eIF3c

eIF3d

eIF3e

eIF3f

eIF3g

eIF3h

eIF3i

eIF3j

eIF3k

Int6

TRIP1

014579

022562

026863

006773

007226

001649

004443

023965

012216

013398

010303

multisubunit complex, binds to 40S

ribosome, eIF4G, eIF1, eIF5

++

++

+

++

++

+

++

++

+

++

+

eIF4A 023083 DEAD-box RNA helicase ++

eIF4B 004840 stimulates helicase ++

eIF4H WBSCR1 008411 stimulates helicase +++

eIF4E1

eIF4E2

eIF4E3

4E-HP

028477

016729

025634

binds to 7mGTP cap, eIF4G ++

+

++

eIF4G 024859 binds to eIF4E, eIF4A, eIF3, PABP ++

eIF5 018897 stimulates eIF2 GTPase +++

eIF5B 001393 ribosome junction, GTPase +

Elongation

eEF1A 000595 delivery of aa-tRNA, GTPase +++

eEF1Balpha

eEF1Bdelta

eEF1Bgamma

015867

000960

002587

GTP exchange activity on eEF1A +

++

++

eEF2 010829 peptidyl-tRNA translocation, GTPase ++

Terminaison

eRF1 023948 recognizes STOP codon ++

eRF3 003213 stimulates eRF1, GTPase +++

Adapted from Morales et al.,

Dev Biol. 2006

Translation factors genes in sea urchin

Une machinerie

De traduction

Complexe

Mais…

identifiée

Mer

&SantéMer

&Santéa: courte présentation de l’Unitéb: traduction & oursinc: vers un réseau traductionnel

Page 16: Ouverture BioTempo TÂCHE 5 : Applications a: courte ...biotempo.genouest.org/data/KickOffCormier2.pdf · Sphaerechinus granularis But what about the translational machinery involved

Adrien Richard

Ouverture BioTempoTÂCHE 5 : Applications

2. Initiation dans le modèle oursin

a: courte présentation de l’Unitéb: traduction & oursinc: vers un réseau traductionnel