CONICET | Buscador de Institutos y Recursos Humanos

INVESTIGADORES

MARTINEZ TOSAR Leandro Julian

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artículos

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Título:

Gene expression in the CNS myelinating cells: RNA binding proteins involved in mRNA localization and translation

Autor/es:

MARTÍNEZ TOSAR LJ, THOMAS MG, SANTA COLOMA TA AND BOCCACCIO GL.

Lugar:

Colonia del Sacramento Uruguay

Reunión:

Jornada; International Society for Neurochemistry /American Society for Neurochemistry Joint Meeting - MYELIN SATELLITE MEETING; 2003

Institución organizadora:

International Society for Neurochemistry /American Society for Neurochemistry

Resumen:

Protein expression in a cell lineage is usually developmentally regulated. A closer analysis reveals that protein synthesis is often spatially restricted inside cells. Thus, cytoplasmic mRNA trafficking is important in modulating gene expression. This is particularly striking in oligodendrocytes, where mRNAs coding for certain myelin proteins are targeted to the cellular processes that enwrap axons. Among the best characterized messengers that concentrate at the myelin sheath assembly sites, we find the mRNAs coding for the highly basic polypeptides MBP and MOBP (Gould et al., 2000). Active mRNA sorting has been largely documented in many organisms and cell types and a common mechanism is emerging. Briefly, an RNA element usually located at the 3´UTR of mRNAs is crucial for targeting (Munro et al., 1999). The formation of a ribonucleoparticle (RNP) precedes translocation, and translation would occur only after reaching the final destination. The outlined mechanism anticipates the participation of a battery of RNA binding proteins that (i) recognize the signal for transport (ii) promote the assembly of the mRNP (iii) mediate the interaction with the transport machinery, namely the cytoskeleton and motor molecules, (iv) repress translation during translocation and (v) anchor the mRNAs allowing translation to proceed (Boccaccio, 2000). We focus in RNA binding proteins putatively involved in RNP formation and messenger silencing such as Testis Brain RNA Binding Protein (TB-RBP) and Staufen. These proteins would participate in distinct aspects of mRNA trafficking, together with the heterogeneous nuclear ribonucleoprotein A2 (hnRNPA2), which was the first trans-acting element to be identified. TB-RBP is involved in mRNA trafficking in neurons. RNA recognition motifs for TB-RBP are present in MBP mRNAs and we have confirmed the expression of this protein in oligodendrocytes by RT-PCR, opening the possibility that TB-RBP may mediate messenger silencing (Boccaccio, 2000). Staufen was initially described in Drosophila and is currently the best characterized example of an RNA binding protein participating in mRNA targeting. It is suspected to play a role in cytoplasmic transport of mRNA in Neurons (Kiebler and DesGrosseillers, 2000). We have recently confirmed its expression in oligodendrocytes. In those cells, Staufen shows a granular distribution spanning the major cellular processes as well as the fine membrane extensions, where myelin targeted mRNAs are located. Furthermore, a family of alternatively spliced Staufen isoforms was identified in our laboratory. The biological significance of these variants is likely related to regulatory aspects of Staufen function. Our hypothesis is that Staufen associates to myelin targeted messengers and participates in the formation of the RNP, thus enabling transport to the myelinating compartment.

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