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Lecture 7

ANAT 262 Lecture Notes - Lecture 7: Nuclear Lamina, Signal Recognition Particle, Nonsense-Mediated Decay


Department
Anatomy & Cell Biology
Course Code
ANAT 262
Professor
John Presley
Lecture
7

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Lecture 7: Nuclear lamins and nuclear pores
Tuesday, February 2, 2016
8:28 AM
Nucleus: approximately size of RBC, 5 um to 10um
Organelle is a membrane-bound compartment that possesses a specific function.
Organization of the nucleus
(1) Nuclear envelope (NE)
Inner and outer nuclear membranes, perinuclear space
Nuclear pore complexes: helps in macromolecules trafficking between cytoplasm
and nucleus
(2) Nuclear lamina: under inner nuclear membrane, related in nuclear diseases
(3) Nucleus interior
Nucleolus
Chromatin: DNA, histones, transcription factors, other proteins
Nuclear bodies: family of compartment identifies by immuno-staining, supply or
process supplying
Nuclear matrix: defined experimentally by extracting nucleus using salt, detergent,
DNases, RNases, what is left is matrix. Contains proteins providing scaffold (skeletal
like) elements in nucleus, provides binding sites for transcription factors
Nucleolus
Compartment that contains lots of different proteins (complex). One major task is
generation of ribosomal subunits. Large subunits have 3 different subunits generated by
initial transcript named 47S into 28S, 5.8S and 5S ribosomal RNA. 5S is transcribed in
nucleus but outside nucleolus. Large ribosomal subunit contains 47 proteins, while small
subunit (18S) has 32 proteins.
Nucleoli have different forms (mostly spherical) and can have different sizes. Nucleoli does
not have a membrane, then how come it stays together?
Proteins like to interact with each other or RNA present in nucleolus. In addition,
nucleolus contains the DNA present that encodes 47S ribosomal RNA. Proteins binds
to this DNA or with each other. Compartment is hence relatively stable. This
principle applies to other compartments in cells.
Functions:
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Nucleoli produce and process 47S ribosomal RNA
Assemble ribosomal subunits
Assemble signal recognition particle (SRP) involved in protein secretion
Regulate apoptosis \control cell cycle progression
Regulate p53 function
Control telemorase function
Regulate stress response
Play a role for the replication of any viruses: viruses take advantage of nucleolus to
replicate
Subcompartments:
A. Granular component: further containing structures
B. Dense fibrillar component; DFC: cleavage of 47S into the smaller subunits, which
then move to granular component, where they are assemble into large subunit
C. Fibrillar component; FC: RNA pol I is sitting at the border of the DFC and FC
which is generating 47S ribosomal RNA.
Nucleolus is considered a highly complex process
Why not translating in the nucleus? mRNA cannot be read in the nucleus, and you do not
want to have proteins in the nucleus unless the cell decide to do so (Dnases in the
nucleus). Proteins made in the nucleus need to be exported, which increase energy
consumption. Maybe there is RNA-DNA hybridization that can happen. Non-sense
mediated decay, mRNA that does not encode proper message, you can degrade it before
it gets translated in the cytoplasm. In the nucleus, you make pre-mRNA, it has to undergo
splicing at different rates. So if you translate before splicing, you can get something
harmful, or pre-mature stop codon. You want to make sure that you only get properly
mature mRNA. You do not want to translate improperly spliced RNA => why you get the
assembly of the ribosomes large and small subunits only in the cytoplasm.
Nuclear pore complexes
Mediate trafficking between cytoplasm and nucleus
Relatively large structures (100 Mda), 8-fold symmetry, contains 1000 proteins (30
different proteins for each slice * 8 copies and some proteins comes in pair.)
Nuclear porins have small sequences that are repeated several times. There are three
major groups, and some of them have repeats or not.
FXF: allows interactions with carrier that move material in and out of nucleus,
proteins trafficking (e.g. NAP62, nuclear porin with mass of 62 kD, Nap53, nap214)
GLFG: important for RNA trafficking (e.g. nap98)
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