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Neural circuits and neuronal pools are two of the main structures found in the nervous system. Neural circuits are networks of neurons that work together to carry out a specific task or process. They consist of interconnected neurons and glial cells, which provide structural and metabolic support.
Neuronal pools are collections of nerve cells with similar functions and interact through chemical and electrical signals. These pools include both interneurons (the central neural circuit nodes that...
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Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
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PIWI-interacting RNAs, or piRNAs, are the most abundant short non-coding RNAs. More than 20,000 genes have been found in humans that code for piRNAs while only 2000 genes have been found for miRNAs. piRNAs can act at the transcriptional and post-transcriptional levels and have a vital role in silencing transposable elements present in germ cells. They are also involved in epigenetic silencing and activation. Previously, they were thought to function only in germ cells but new evidence suggests...
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Ribosome synthesis is a highly complex and coordinated process involving more than 200 assembly factors. The synthesis and processing of ribosomal components occurs not only in the nucleolus but also in the nucleoplasm and the cytoplasm of eukaryotic cells.
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In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
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In the CNS, neurogenesis, the birth of new neurons from stem cells, is limited to the hippocampus in adults. In other regions of the brain and spinal cord, neurogenesis is almost non-existent due to inhibitory influences from neuroglia, especially oligodendrocytes, and the absence of growth-stimulating cues. The myelin produced by oligodendrocytes in the CNS inhibits neuronal regeneration. Furthermore, astrocytes proliferate rapidly after neuronal damage, forming scar tissue that physically...
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Los ARN de elementos repetidos integran un circuito de crecimiento neuronal

Eitan Erez Zahavi1, Indrek Koppel2, Riki Kawaguchi3

  • 1Departments of Biomolecular Sciences and Molecular Neuroscience, Weizmann Institute of Science, Rehovot, Israel.

Cell
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Resumen

Los B2-SINE inductores de crecimiento recientemente identificados (GI-SINE) promueven el crecimiento axonal después de una lesión neuronal. Estos elementos transponibles vinculan la transcripción génica con la traducción local del ARN, crucial para la regeneración neuronal.

Palabras clave:
Localización del ARNElementos nucleares cortos intercaladoscrecimiento del axónEl transporte axonaltraducción locallesión del nerviodetección de longitud neuronalARN no codificante

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Área de la Ciencia:

  • La neurociencia
  • Biología molecular
  • La genética

Sus antecedentes:

  • El crecimiento neuronal y la regeneración dependen de la traducción local de ARNm dentro de los axones.
  • Comprender los mecanismos moleculares que regulan la reparación axonal es fundamental para el tratamiento de lesiones neurológicas.

Objetivo del estudio:

  • Para investigar los cambios en la poliadenilación del ARN después de la lesión de la neurona sensorial.
  • Identificar nuevos elementos involucrados en la regulación de la regeneración axonal.

Principales métodos:

  • Análisis de la poliadenilación del ARN en las neuronas sensoriales lesionadas.
  • Inducción y expresión de los elementos de repetición B2-SINE (GI-SINE).
  • Evaluación del crecimiento axonal en varios modelos neuronales (sensoriales, retinales y corticospinales).
  • Investigación de las interacciones GI-SINE con las proteínas ribosómicas y la nucleolina.
  • El uso de oligonucleótidos antisenso para interrumpir la función GI-SINE.

Principales resultados:

  • Upregulación de elementos de repetición B2-SINE poliadenilados específicos (GI-SINE) en las neuronas sensoriales lesionadas.
  • Los GI-SINEs son inducidos por los loci asociados al promotor AP-1.
  • La expresión GI-SINE exógena promueve el crecimiento axonal en múltiples tipos neuronales.
  • Los GI-SINEs interactúan con las proteínas ribosómicas y la nucleolina para modular la traducción citoplasmática.
  • La inhibición antisentido de GI-SINEs afecta el crecimiento de las neuronas sensoriales y las interacciones nucleolina-ribosoma.

Conclusiones:

  • Una subfamilia específica de elementos transponibles, GI-SINEs, juega un papel integral en la regeneración neuronal.
  • Los GI-SINEs conectan los factores de transcripción AP-1 con el mecanismo de traducción de ARN localizado en las neuronas.
  • Estos hallazgos revelan un nuevo circuito regulador para el crecimiento y la reparación axonal.