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Chapter 9
Nucleus
16
Biology
Undergraduate 4
03/01/2014

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Term
Describe the nuclear envelope

1. Function
2. Structure
3. Permeability
Definition
1. separates the nucleus from cytoplasm
-act as barrier
2. two membranes with underlying nuclear lamina
-perinuclear space in between
-same as lumen of ER
3. only permeable to small non polar molecules
-nuclear pores are only channels for passage
Term
Describe the nuclear envelope

1. Outer membrane
2. Inner membrane
Definition
1. connected directly to ER
-contains ribosomes and is functionally similar to ER
-enriched in membrane proteins to bind to cytoskeleton

2. contains proteins specific to nucleus
-bind to nuclear lamina
Term
Describe the nuclear lamina

1. Definition
2. Structure
3. Inner membrane binding
Definition
1. fibrous mesh of proteins called lamins that provides structural support
-lamins dissolve in mitosis
-mutation in lamins lead to progeria

2. 3 lamin genes (A,B,C) code for 7 proteins
-2 lamins interact to form dimer where alpha helical regions combine to form coil

3. bind to inner membrane proteins such as Emerin and Lamin B receptor
-lamins bind to lamin associated proteins that bind to chromatin
-also extend into nucleus
Term
Describe the nuclear pore complex

1. Function
2. Structure
Definition
1. only channels that polar molecules, ions, and RNA can pass through
-RNA has to leave and TFs have to enter
-smaller molecules pass freely through
-macros pass through central pore by active process

2. large structure made of 30 different proteins (nucleoporins)
-8 fold symmetry (spoke rings) with large central channel
-protein filaments extend from the rings forming basket-like structure on nuclear side to bring proteins in
-other filaments outside nucleus
*these filaments have AA that code for nuclear transport
Term
Describe nuclear localization signals
Definition
-stretch of AA that code for nuclear transport
-some stretches are continuous and some are bipartite

ex. SV40 T ag is 7 AA
ex. Nucleopasmin is separated by 10 AA but fold together
Term
Describe importins and Ran
Definition
-receptors that recognize nuclear localization signals
-importins are regulated by Ran that binds to GTP
Term
Describe the process of nuclear transport and Ran

a. Setting
b. Process
Definition
a. outside: GAP that cleaves ATP->ADP so there is a higher concentration of ADP outside
inside: GEF takes GDP->GTP so there is more ATP inside

b. 1. importins bind to nuc loc sigs
2. importin binds to cytoplasmic filaments on nuc pore
3. importin binds to proteins throughout pore (Phe-Gly repeats)
4. importin/cargo complex is disrupted by Ran/GTP
-cargo is released into nucleus
5. importin and Ran/GTP go out because of concen gradient
6. GAP hydrolyzes GTP->GDP and importin in released
7. Ran/GDP goes back into nucleus by NTF2 and Ran/GTP is regenerated by GEF
Term
Describe protein export from nucleus
Definition
Exportins instead of importins
-bind to similar AA sequence as nuc log sig (nuc exp sig)
-belong to family called karyopherins

1. Ran/GTP promotes binding to exportins
2. Ran/GDP dissociates complex
*opposite of importins
Term
Describe nuclear import regulation by phosphorylation
Definition
Yeast TF Pho4
1. phosphorylated at Ser next to nuc loc sig and causes interference
2. can't be imported and can't be TF
3. those genes are then turned off
*can be reversed
Term
Describe RNA transport out of nucleus
Definition
-most RNAs are export to cytoplasm
-active, energy dependent process
-RNAs are transported across as RNP complexes
-snRNAs function inside nucleus
Term
Describe internal organization of nucleus: chromatin
Definition
-genetic material is organized to localize function
-lamins attach to chromatin
-heterochromatin is tightly packed but euchromatin is de condensed and distributed throughout nucleus
-euchromatin is placed together so TFs can access

Constitutive Heterochromatin: not transcribed at all (centromeres)
Facultative: not transcribed in particular cells

-localized into specific territories that is consistent
-Actively transcribed genes are located at periphery
Term
Describe internal organization of nucleus: DNA replication and mRNA splicing
Definition
DNA: replication takes place at clustered site
-replication factories are distinct functional bodies with multiple replication forks

mRNA: splicing machinery is concentrated in discrete nuclear bodies called nuclear speckles
-staining snRNPs

PMLs: collection of TFs and chromatin modifying proteins
Term
Describe the nucleolus: composition
Definition
-site of rRNA transcription and processing and some assembly of ribosomes
-no membrane
-associate with rRNAs: 5.8, 18, 28S and transcribe with RNA poly 1
-all cells have multiple rRNA gene copies
Term
Describe the nucleolus: structure
Definition
3 regions
1. fibrillar center 2. dense fibrillar component 3. granular

-after transcription of 45S pre-rRNA they form one large cluster
Term
Describe the nucleolus: rRNA processing
Definition
-series of cleavages like mRNA
-addition of methyl groups and conversion of uridine
-snoRNAs function in processing (spliceosomes)
Term
Describe the nucleolus: ribosome assembly
Definition
-ribosomal proteins are transcribed outside nucleus and transported back in
-5s are transcribed outside nucleolus
-release both subunits into cytoplasm
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