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Spatial codes in dendritic BC1 RNA.

Muslimov IA, Iacoangeli A, Brosius J, Tiedge H - J. Cell Biol. (2006)

Bottom Line: This element features a GA kink-turn (KT) motif that is indispensable for distal targeting.It specifically interacts with heterogeneous nuclear ribonucleoprotein A2, a trans-acting targeting factor that has previously been implicated in the transport of MBP mRNA in oligodendrocytes and neurons.Our work suggests that a BC1 KT motif encodes distal targeting via the A2 pathway and that architectural RNA elements, such as KT motifs, may function as spatial codes in neural cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Pharmacology, The Robert F. Furchgott Center for Neural and Behavioral Science, State University of New York Health Science Center at Brooklyn, Brooklyn, NY 11203, USA.

ABSTRACT
BC1 RNA is a dendritic untranslated RNA that has been implicated in local translational control mechanisms in neurons. Prerequisite for a functional role of the RNA in synaptodendritic domains is its targeted delivery along the dendritic extent. We report here that the targeting-competent 5' BC1 domain carries two dendritic targeting codes. One code, specifying somatic export, is located in the medial-basal region of the 5' BC1 stem-loop structure. It is defined by an export-determinant stem-bulge motif. The second code, specifying long-range dendritic delivery, is located in the apical part of the 5' stem-loop domain. This element features a GA kink-turn (KT) motif that is indispensable for distal targeting. It specifically interacts with heterogeneous nuclear ribonucleoprotein A2, a trans-acting targeting factor that has previously been implicated in the transport of MBP mRNA in oligodendrocytes and neurons. Our work suggests that a BC1 KT motif encodes distal targeting via the A2 pathway and that architectural RNA elements, such as KT motifs, may function as spatial codes in neural cells.

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Differential electrophoretic mobilities of 5′ BC1 derivatives on native PAGE. Conversion of the apical KT motif (IL-A) to a WC helical stem and elimination of the single-U bulge (B22) both resulted in substantially increased relative mobilities. Highest relative mobility was observed with the IL-A:WC/ΔU double mutant. See Fig. 1 for motif abbreviations.
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fig6: Differential electrophoretic mobilities of 5′ BC1 derivatives on native PAGE. Conversion of the apical KT motif (IL-A) to a WC helical stem and elimination of the single-U bulge (B22) both resulted in substantially increased relative mobilities. Highest relative mobility was observed with the IL-A:WC/ΔU double mutant. See Fig. 1 for motif abbreviations.

Mentions: We compared the mobility of the wild-type 5′ BC1 domain with that of a mutant domain in which the noncanonical base pairs of the GA apical internal loop motif have been replaced with standard WC base pairs (IL-A:WC). We observed that the WC mutant 5′ BC1 domain displays a considerably increased mobility, relative to the wild-type 5′ domain (Fig. 6, compare lanes 1 and 3). The data indicate that a KT in the wild-type domain has been eliminated in the mutant domain, resulting in a now “straightened” helical stem with higher mobility. Thus, the results corroborate our hypothesis that a KT motif is introduced by the GA apical internal loop. Because conversion of the noncanonical base pairs in this motif to standard WC base pairs results in a loss of distal dendritic targeting competence (Fig. 4 A), the combined results suggest that a code specifying distal dendritic targeting is expressed by a KT internal loop motif residing in the apical 5′ BC1 domain. We will henceforth refer to this motif as KT BC1.


Spatial codes in dendritic BC1 RNA.

Muslimov IA, Iacoangeli A, Brosius J, Tiedge H - J. Cell Biol. (2006)

Differential electrophoretic mobilities of 5′ BC1 derivatives on native PAGE. Conversion of the apical KT motif (IL-A) to a WC helical stem and elimination of the single-U bulge (B22) both resulted in substantially increased relative mobilities. Highest relative mobility was observed with the IL-A:WC/ΔU double mutant. See Fig. 1 for motif abbreviations.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1808587&req=5

fig6: Differential electrophoretic mobilities of 5′ BC1 derivatives on native PAGE. Conversion of the apical KT motif (IL-A) to a WC helical stem and elimination of the single-U bulge (B22) both resulted in substantially increased relative mobilities. Highest relative mobility was observed with the IL-A:WC/ΔU double mutant. See Fig. 1 for motif abbreviations.
Mentions: We compared the mobility of the wild-type 5′ BC1 domain with that of a mutant domain in which the noncanonical base pairs of the GA apical internal loop motif have been replaced with standard WC base pairs (IL-A:WC). We observed that the WC mutant 5′ BC1 domain displays a considerably increased mobility, relative to the wild-type 5′ domain (Fig. 6, compare lanes 1 and 3). The data indicate that a KT in the wild-type domain has been eliminated in the mutant domain, resulting in a now “straightened” helical stem with higher mobility. Thus, the results corroborate our hypothesis that a KT motif is introduced by the GA apical internal loop. Because conversion of the noncanonical base pairs in this motif to standard WC base pairs results in a loss of distal dendritic targeting competence (Fig. 4 A), the combined results suggest that a code specifying distal dendritic targeting is expressed by a KT internal loop motif residing in the apical 5′ BC1 domain. We will henceforth refer to this motif as KT BC1.

Bottom Line: This element features a GA kink-turn (KT) motif that is indispensable for distal targeting.It specifically interacts with heterogeneous nuclear ribonucleoprotein A2, a trans-acting targeting factor that has previously been implicated in the transport of MBP mRNA in oligodendrocytes and neurons.Our work suggests that a BC1 KT motif encodes distal targeting via the A2 pathway and that architectural RNA elements, such as KT motifs, may function as spatial codes in neural cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Pharmacology, The Robert F. Furchgott Center for Neural and Behavioral Science, State University of New York Health Science Center at Brooklyn, Brooklyn, NY 11203, USA.

ABSTRACT
BC1 RNA is a dendritic untranslated RNA that has been implicated in local translational control mechanisms in neurons. Prerequisite for a functional role of the RNA in synaptodendritic domains is its targeted delivery along the dendritic extent. We report here that the targeting-competent 5' BC1 domain carries two dendritic targeting codes. One code, specifying somatic export, is located in the medial-basal region of the 5' BC1 stem-loop structure. It is defined by an export-determinant stem-bulge motif. The second code, specifying long-range dendritic delivery, is located in the apical part of the 5' stem-loop domain. This element features a GA kink-turn (KT) motif that is indispensable for distal targeting. It specifically interacts with heterogeneous nuclear ribonucleoprotein A2, a trans-acting targeting factor that has previously been implicated in the transport of MBP mRNA in oligodendrocytes and neurons. Our work suggests that a BC1 KT motif encodes distal targeting via the A2 pathway and that architectural RNA elements, such as KT motifs, may function as spatial codes in neural cells.

Show MeSH