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Figure 9-2 Molecular Biology of the Cell (© Garland Science 2008)

Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

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Page 1: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

Figure 9-2 Molecular Biology of the Cell (© Garland Science 2008)

Page 2: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

Figure 9-24 Molecular Biology of the Cell (© Garland Science 2008)

Page 3: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

Figure Q9-3 Molecular Biology of the Cell (© Garland Science 2008)

Page 4: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

Figure 9-14 Molecular Biology of the Cell (© Garland Science 2008)

Page 5: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

Figure 9-13 Molecular Biology of the Cell (© Garland Science 2008)

Page 6: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

Figure 9-15 Molecular Biology of the Cell (© Garland Science 2008)

Page 7: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

Figure 9-18 Molecular Biology of the Cell (© Garland Science 2008)

Page 8: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

Figure 9-21 Molecular Biology of the Cell (© Garland Science 2008)

Page 9: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

Figure 9-20 Molecular Biology of the Cell (© Garland Science 2008)

Page 10: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

Figure 9-22 Molecular Biology of the Cell (© Garland Science 2008)

Page 11: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

Figure 9-17 Molecular Biology of the Cell (© Garland Science 2008)

Page 12: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

Drugs  can  affect  filament  assembly

Page 13: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

A PAR-1–dependent orientation gradient of dynamic microtubules directs posterior cargo transport in the

Drosophila oocyte

Richard M. Parton, Russell S. Hamilton, Graeme Ball, Lei Yang, C. Fiona Cullen, Weiping Lu, Hiroyuki Ohkura, and Ilan Davis

JCB Volume 194(1):121-135

July 11, 2011

© 2011 Parton et al.

Page 14: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

A dynamic network of MTs extends throughout the oocyte posterior.

Parton R et al. JCB 2011;194:121-135

© 2011 Parton et al.

Page 15: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

EB1 tracks the plus ends of dynamic MTs throughout the oocyte.

Parton R et al. JCB 2011;194:121-135

© 2011 Parton et al.

Page 16: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

Staufen protein is transported on MTs at the oocyte posterior.

Parton R et al. JCB 2011;194:121-135

© 2011 Parton et al.

Page 17: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

Analysis of EB1 trajectories reveals a graded bias in MT orientation.

Parton R et al. JCB 2011;194:121-135

© 2011 Parton et al.

Page 18: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

MT nucleation occurs at discrete foci along the cortex but is absent from the posterior.

Parton R et al. JCB 2011;194:121-135

© 2011 Parton et al.

Page 19: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

MTs are nucleated around the entire posterior in par-1 hypomorphic mutant oocytes, abolishing the orientation bias.

Parton R et al. JCB 2011;194:121-135

© 2011 Parton et al.

Page 20: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

A biased random organization of MTs in the oocyte delivers cargoes to the posterior.

Parton R et al. JCB 2011;194:121-135

© 2011 Parton et al.

Page 21: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

Figure 7-5 Molecular Biology of the Cell (© Garland Science 2008)

Page 22: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

Figure 7-92 Molecular Biology of the Cell (© Garland Science 2008)

Page 23: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

Figure 7-94 Molecular Biology of the Cell (© Garland Science 2008)

Page 24: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

Figure 7-95 Molecular Biology of the Cell (© Garland Science 2008)

Page 25: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

Figure 7-96 Molecular Biology of the Cell (© Garland Science 2008)

Page 26: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

Figure 7-97 Molecular Biology of the Cell (© Garland Science 2008)

Page 27: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

Figure 7-98 Molecular Biology of the Cell (© Garland Science 2008)

Page 28: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

Figure 7-106 Molecular Biology of the Cell (© Garland Science 2008)

Page 29: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

Figure 7-110 Molecular Biology of the Cell (© Garland Science 2008)

Page 30: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

Figure 7-112 Molecular Biology of the Cell (© Garland Science 2008)

Page 31: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

The Fate of mRNA Loaded With the miRISC

Targeted mRNA accumulates in P bodies

mRNA is stored in P bodies, undergoes degradation, or reenters the translation pathway

from Rana, Nature Rev.Mol.Cell Biol. 8, 23 (2007)

Page 32: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

miRNAs Promote mRNA Deadenylation

from Huntzinger and Izaurralde, Nature Rev.Genet. 12, 99 (2011)

miRNA guide strand associates with AGO

AGO interacts with GW182

GW182 may compete with eIF4G for binding to PABPC and prevents mRNA circularization

Assembly of AGO-GW182-PABPC complex triggers deadenylation by CAF1-CCR4-NOT

GW182 may reduce the affinity of PABPC for the poly(A) tail

Page 33: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

Fate of Deadenylated mRNAs

from Huntzinger and Izaurralde, Nature Rev.Genet. 12, 99 (2011)

Deadenylated mRNAs are stored in a translationally repressed state

Deadenylated mRNAs are decapped by DCP2 associated with decapping activators

Decapped mRNA is degraded by XRN1

Page 34: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

Overview of RNA-Mediated Gene Silencing

from Eulalio et al., Nature Rev.Mol.Cell Biol. 8, 9 (2007)

siRNA triggers endonucleolytic cleavage of perfectly-matched complementary targets

The resulting mRNA fragments are degraded

miRNA triggers accelerated deadenylation and decapping of partially-complementary targets and requires Argonaute proteins and a P-body component

Cleavage is catalyzed by Argonaute proteins

miRNA represses translation

siRNA

miRNA

Page 35: Figure 9-2 Molecular Biology of the Cell (© Garland ...biology.hunter.cuny.edu/cellbio/Feinstein Cell bio 2014/Bratu... · Overview of RNA-Mediated Gene Silencing from Eulalio et

A MicroRNA Regulates Neuronal Differentiation by Controlling Alternative Splicing

miR-124 targets a component of a repressor of neuron-specific genes

miR-124 results in reduced expression of PTBP1 leading to the accumulation of PTBP2

PTBP2 results in a global switch to neuron- specific alternative splicing patterns

from Makeyev et al., Mol.Cell 27, 435 (2007)