nucleolar sequestration
DESCRIPTION
NUCLEOLAR SEQUESTRATION . - PowerPoint PPT PresentationTRANSCRIPT
The nucleolus is known to capture and immobilize proteins, then are unable to diffuse and to interact with their binding partners. Targets of this post-translational regulatory mechanism include hTERT. It is now known that noncoding RNAs originating from intergenic regions of the nucleolus are responsible for this phenomenon.
NUCLEOLAR SEQUESTRATION
SUB NUCLEAR BODIES 1. Cajal bodies,
2. Gemini of coiled bodies
3. Polymorphic interphase karyosomal
association (pika)
4. Promyelocytic leukaemia (PML) bodies,
5. Paraspeckles,
6. Splicing speckles.
as part of abnormal disease processes. NEMALINE MYOPATHY: the presence of small intranuclear rods has been reported , mutations in actin, and the rods themselves consist of mutant actin as well as other cytoskeletal proteins.
Structure name Diameter
Cajal bodies 0.2–2.0 µm
PIKA 5 µm
PML bodies 0.2–1.0 µm
Paraspeckles 0.2–1.0 µm
Speckles 20–25 nm
CAJAL BODIES/ coiled bodies
By Santiago Ramón y Cajal in 1903
1 to 10
Tangle of coiled threads and are
characterized by the presence
of the p80 coilin protein.
Nucleus of proliferative cells like
embryonic cells and tumor cells, or
metabolically active cells like neurons.
fusion of p80/Coilin protein to GFP
Number of different roles relating to RNA maturation
processing, biogenesis and trafficking of small nucleolar RNA
(snoRNA) and small nuclear RNA (snRNA), and histone mRNA
modification
Contribute to the biogenesis of telomerase enzyme, and assist
in subsequent transport of telomerase to telomeres.
"twin" relationship with CBs
Gems are similar in size and shape to CBs, and in fact are
virtually indistinguishable under the microscope
Gems do not contain small nuclear ribonucleoproteins (snRNPs),
but do contain protein called survivor of motor neurons (SMN)
(whose function relates to snRNP biogenesis) and Gemin 2
GEMINI OF COILED BODIES/ GEMS
Believed to assist CBs in snRNP biogenesis, though it has also been
suggested from microscopy evidence that CBs and gems are different
manifestations of the same structure
SPINAL MUSCULAR ATROPHY, a motor neuron disorder, results
from reduced levels or a mutation in the SMN protein.
Nuclear domain 10 (ND10), Kremer bodies, and PML oncogenic domains
PML bodies/ Promyelocytic leukaemia
Acute promyelocytic leukaemia (APL) , translocation of
PML gene (chr 15) to the gene encoding the alpha-retinoic acid
receptor (chr 17), resulting in the production of a fusion protein.
• Hybrid protein binds with enhanced affinity to sites on the cell's
DNA, blocking transcription and differentiation of granulocytes,
accumulating immature granulocytes called promyelocytes.
• Cells from these individuals exhibit fragmented PML bodies.
Treatment with retinoic acid results in cancer remission and the
restoration of normal PML body structure.
Spherical bodies found scattered throughout the nucleoplasm, 10-
30 in number,
Major component, the Promyelocytic leukemia protein.
They are often seen in the nucleus in association with Cajal
bodies.
recruit an ever-growing number of proteins, thus may play a
role in transcriptional regulation and in anti-viral responses.
pml-/- mice cannot assemble nuclear bodies, develop normally
and live well, demonstrating that PML bodies are dispensable for
most basic biological functions.
25-50 in number
Enriched in pre-messenger RNA splicing factors
located in the interchromatin regions of the
nucleoplasm of mammalian cells. thought to act as a reservoir for the
splicing of nascent pre-mRNA at nearby genes.
irregular, punctate structures (point like depressions) which vary in size
and shape, seen as clusters of interchromatin granules under EM.
SPLICING SPECKLES
Speckles are dynamic structures, and both their protein and RNA-
protein components can cycle continuously between speckles and
other nuclear locations, including active transcription sites.
Because of a cell's changing requirements, the composition and
location of these bodies changes according to mRNA transcription
and regulation
Discovered by Fox et al. in 2002
"para" is short for parallel and the "speckles" refers to the splicing
speckles to which they are always in close proximity.
irregularly shaped compartments in the nucleus' interchromatin
space.
PARASPECKLES
First documented in HeLa cells, 10–30 per nucleus, exist in all human
primary cells, transformed cell lines
In the cell cycle, during telophase, no RNA Pol II transcription ,
paraspeckle disappears and all of its associated protein components
form a crescent shaped perinucleolar cap in the nucleolus.
suggests to mediate regulatory cross talk. Many other proteins
involved in Pol II transcription are also observed within perinucleolar
caps in cells where Pol II transcription is inactive
Archa H. Fox….
were first described in microscopy studies
in 1991.
visible by phase contrast alone as a region
of decreased density.
The morphology of this region changes
dramatically during the cell cycle.
The function of the PIKA is not yet
known,
though they were not thought to be
associated with active DNA replication,
transcription, or RNA processing.
PIKA (POLYMORPHIC INTERPHASE KARYOSOMAL ASSOCIATION)
The function of nucleus can be estimated from the following
statement.
Nucleus is the storehouse of genes and genes dictate the cell to
perform specialized functions such as cell division, cell sectretion,
cell communication, etc. Removal of nucleus from a cell means
removal of guiding entities of that cell. Therefore, without nucleus,
a cell can neither survive, nor show specialized activities.
FUNCTIONS OF NUCLEUS