nucleolar sequestration

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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

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Page 1: NUCLEOLAR SEQUESTRATION

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

Page 2: 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

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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

Page 5: NUCLEOLAR SEQUESTRATION

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.

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"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.

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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.

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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.

Page 9: NUCLEOLAR SEQUESTRATION

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

Page 10: NUCLEOLAR SEQUESTRATION

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

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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

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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….

Page 14: NUCLEOLAR SEQUESTRATION

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)

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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