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NUCLEOLAR SEQUESTRATION

NUCLEOLAR SEQUESTRATION .

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NUCLEOLAR SEQUESTRATION

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  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.

  2. SUB NUCLEAR BODIES Cajal bodies, Gemini of coiled bodies Polymorphic interphasekaryosomal association (pika) Promyelocytic leukaemia (PML) bodies, Paraspeckles, 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.

  3. 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

  4. 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.

  5. GEMINI OF COILED BODIES/ GEMS "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 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.

  6. PML bodies/ Promyelocytic leukaemia Nuclear domain 10 (ND10), Kremer bodies, and PML oncogenic domains • Acute promyelocyticleukaemia (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.

  7. 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.

  8. SPLICING SPECKLES 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.

  9. 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

  10. PARASPECKLES 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.

  11. 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 RNAPol 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….

  12. PIKA (POLYMORPHIC INTERPHASE KARYOSOMAL ASSOCIATION) 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.

  13. FUNCTIONS OF NUCLEUS 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.

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