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Jonathan Cardona Vélez. Medicine student. III Semester. Medellín - Colombia. 2010.

Plegable Molecular biology

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Text of Plegable Molecular biology

  • 1. Jonathan Cardona Vlez. Medicine student. III Semester. Medelln - Colombia. 2010.

2. 3. 4. The nuclear pore complex (NPC) is emerging as an important regulator of gene expression, as the production of translationally competent mRNAs requires transcription, post-transcriptional processing, NPC docking and translocation across the NPC. Proximal spinal muscular atrophy is caused by deficiency of the survival motor neuron (SMN) protein, this is expressed and localized to nuclear complex known as Gemini of coiled bodiesand its function is related to small nuclear ribonucleoproteins (snRNPs)biogenesis. 5. Traffic between the nucleus and the cytoplasm is accomplished through nuclear membranes across specialized circular apertures. These apertures are filled with cylindrical macromolecular assemblies termed nuclear pore complexes (NPCs);but that is not its only function, recent evidence says, the nuclear envelope can also promote the activation of genes. 6. Each NPC is a cylindrical structure comprised of eight spokes surrounding a central tube that connects the nucleoplasm and cytoplasm. The outer and inner nuclear membranes (ONM and INM, respectively) of the nuclear envelope join to form grommets in which the NPC sits. Transport of almost all macromolecules into and out of the nucleus is achieved through a common active mechanism that requires the assistance of soluble nuclear transport factors (NTFs) and transport signals, which together form the soluble phase of nuclear transport. 7. The NPC is freely permeable to small molecules, metabolites and ions, but acts as a highly efficient molecular sieve for macromolecules; this being its main function.At the NPC, the nucleus and cytoplasm are connected by a channel, which is filled with flexible, filamentous Phe-Gly nucleoporins (FG Nups). Spurious macromolecules are physically excluded from entering the densely packed FG Nup meshwork.NTF-bound cargo can enter the channel from either its cytoplasmic or nucleoplasmic side and hop between binding sites on the FG Nups until they return to the original compartment or reach the opposite side of the NPC. 8. NPC associates with numerous molecules and structures in the cytoplasm and nucleoplasm through its cytoplasmic filaments and nuclear basket, respectively.Basket components seem to be involved in the mechanism of mRNA surveillance, which prevents defective mRNAs, such as unspliced or partially spliced polyadenylated RNA molecules, from reaching the cytoplasm. Many of the factors involved in mRNP maturation and export have also been implicated in the recruitment of active genes to the NPC. 9. I think this article is very important because it provides new insights to advance in the regulation of functional products of a specific gene,which is constituted as a work multidisciplinary and of great medical importance to be able to develop techniques to prevent and fight diseases even before its appearance. 10. Proximal spinal muscular atrophy (SMA) is the predominant form of motor neuron disease in children and young adults. This disease is caused by homozygous deletion or mutation of the SMN1 gen on human chromosome 5, as consequence, two functional copies of the SMN gen are found in humans; SMN1 and SMN2 genes. 11. The SMN1 and SMN2 genes differ by five nucleotide exchanges, two of them within exons. In most transcripts derived from the SMN2 gene, a translationally silent cytosine to thymidine exchange at position 6 of exon 7 is responsible for the skipping of exon 7 during splicing.This mutation abolishes an exonic splice enhancer site (ESE)7 and generates a new exonic splicing silencer domain for the last coding exon of the SMN gene.In SMA, the prevailing symptom is proximal skeletal muscle weakness stemming from degeneration of spinal and bulbar motor neurons. 12. The resulting SMN protein lacks the C-terminal 16 amino acid residues, which are replaced by four amino acids encoded by exon 8 sequences. The corresponding protein is less stable, and the altered C terminus of the SMN protein cannot self-associate anymore, making it less active. As a consequence, the SMN2 gene cannot fully compensate for deficiency of the SMN1 gene. However, some transcripts from the SMN2 gene that include the exon 7encoded domain do undergo correct alternative splicing, so that 10% to 30% of functional full-length SMN proteins are produced from the SMN2 gene. 13. Targets for therapy are marked as red circles. Increase of SMN2 promoter activity gives rise to enhanced production of truncated SMN27 mRNA, but also to enhanced production of SMN2 full-length mRNA and SMN protein. Restoration of splicing and inclusion of exon 7 by means of antisense oligonucleotides forms a second target for therapy development.Schematic diagram of the SMN1 and SMN2 genes on human chromosome (chr.) 5.SMN protein is normally found in both the nucleus and the cytoplasm of spinal motor neurons (right); the deficit in SMN expression (left) depletes SMN immunoreactivity in both regions. 14. I find very interesting advance in the treatment of a disease from understandingthe underlying molecular process, as this facilitates the comprehension and treatment of other disorders of importance,especially neurodegenerative diseases; also opens the door to a deeper approach than is the cell dynamics. 15. From the advances in understanding and manipulating genes will becreatedmore conditions that scientist can alter a person's genetic material to fight or prevent disease. 16. This work may help develop techniques to prevent and fight diseases, even before its appearance, everything from the molecular level, which makes these techniques are more selective and efficient. 17. A better knowledge of the cellular dysfunction in SMA, couldhelp to pave the way toward therapies for the treatment of neurodegenerative disorders where synapse dysfunction and loss is a pathophysiological hallmark that correlates with disease symptoms. 18. The progress in this area is a general issue applicable for the treatment of other neurodegenerative disorders where the blood-brain barrier is a major consideration, such as amyotrophic lateral sclerosis , Alzheimer's disease. 19.

  • Martnez LM. El ncleo, estructura y funcin. Martnez LM. Biologa molecular. 5. ed. Medelln: Universidad Pontificia Bolivariana; 2009. p. 43-50.
  • Strambio-De-Castillia C, Niepel M, Rout MP. The nuclear pore complex: bridging nuclear transport and gene regulation. Nat Rev Mol Cell Biol. 2010 Jul; 11(7):490-501.
  • Sendtner M. Therapy development in spinal muscular atrophy. Nat Neurosci. 2010 Jul; 13(7):795-9.

20. Riberas del Sena, 1887. Van Gogh. Van Gogh museum,msterdam .