Limits...
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.

Show MeSH
The BC1 KT motif (KT BC1). Two general classes of KT motifs have been described, the classic KT and the minimal KT (Vidovic et al., 2000; Klein et al., 2001; Hardin and Batey, 2004). KT BC1 belongs to a subtype of the classic KT that is exemplified by KT-58 in 23S rRNA. MBP, CaMKIIα, and PKMζ mRNA contain in their respective 3′ UTRs classic KT motifs that match consensus (Tiedge, 2006). R, purine; N, any nucleotide; blue, canonical G-C pairs of the C-stem; red, noncanonical G·A pairs of the NC-stem; orange, nominally unpaired internal loop nucleotides, may engage in stacking and trans–Sugar-Edge/Sugar-Edge interactions; yellow, extruded nucleotide. Motifs are aligned with their C-stems (blue, G-C pairs) to the left, NC-stems (red, G·A pairs) to the right of the asymmetric internal loop. In the consensus KT, the transitional position between the NC-stem and the resumption of A-form helical structure by G-C base pairs (referred to as N·N) may be occupied by an intervening base pair, by an unpaired residue, or not at all. KTs in small untranslated RNAs often carry a G·U wobble pair in this position (Rozhdestvensky et al., 2003; Hamma and Ferré-D'Amaré, 2004), although a sheared (trans–Hoogsteen/Sugar Edge) G·U pair is also allowed (Lescoute et al., 2005). Flanking G-C base pairs may occur in either the G-C or the C-G orientation. In the KT-58 subtype (including KT BC1), internal loop G and C nucleotides may also be part of an extended C-stem (Lescoute et al., 2005) and can therefore be rendered in either color coding.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC1808587&req=5

fig9: The BC1 KT motif (KT BC1). Two general classes of KT motifs have been described, the classic KT and the minimal KT (Vidovic et al., 2000; Klein et al., 2001; Hardin and Batey, 2004). KT BC1 belongs to a subtype of the classic KT that is exemplified by KT-58 in 23S rRNA. MBP, CaMKIIα, and PKMζ mRNA contain in their respective 3′ UTRs classic KT motifs that match consensus (Tiedge, 2006). R, purine; N, any nucleotide; blue, canonical G-C pairs of the C-stem; red, noncanonical G·A pairs of the NC-stem; orange, nominally unpaired internal loop nucleotides, may engage in stacking and trans–Sugar-Edge/Sugar-Edge interactions; yellow, extruded nucleotide. Motifs are aligned with their C-stems (blue, G-C pairs) to the left, NC-stems (red, G·A pairs) to the right of the asymmetric internal loop. In the consensus KT, the transitional position between the NC-stem and the resumption of A-form helical structure by G-C base pairs (referred to as N·N) may be occupied by an intervening base pair, by an unpaired residue, or not at all. KTs in small untranslated RNAs often carry a G·U wobble pair in this position (Rozhdestvensky et al., 2003; Hamma and Ferré-D'Amaré, 2004), although a sheared (trans–Hoogsteen/Sugar Edge) G·U pair is also allowed (Lescoute et al., 2005). Flanking G-C base pairs may occur in either the G-C or the C-G orientation. In the KT-58 subtype (including KT BC1), internal loop G and C nucleotides may also be part of an extended C-stem (Lescoute et al., 2005) and can therefore be rendered in either color coding.

Mentions: Our data suggest that the KT BC1, which is located in the apical 5′ BC1 domain, serves as a long-range targeting code. A search algorithm (see Materials and methods) identified similar KT motifs in the DTEs of several targeted neural RNAs (see Discussion). Therefore, we hypothesized that a trans-acting factor (i.e., a decoding protein) that recognizes such KT motifs would interact with those RNAs that use them as spatial codes. One of the KT motifs identified by our search algorithm is located in the 3′ UTR of myelin basic protein (MBP) mRNA, an mRNA that is distally targeted in oligodendrocytes and neurons (Ainger et al., 1993; Shan et al., 2003). This KT MBP motif (Fig. 9) overlaps with a previously described 21-nt element in the MBP 3′ UTR that was initially recognized as an RNA transport signal (Ainger et al., 1997). It was later identified as a targeting-determinant response element for hnRNP A2 (A2RE; Hoek et al., 1998; Munro et al., 1999; Shan et al., 2000, 2003). We therefore reasoned that hnRNP A2 may also interact with KT BC1.


Spatial codes in dendritic BC1 RNA.

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

The BC1 KT motif (KT BC1). Two general classes of KT motifs have been described, the classic KT and the minimal KT (Vidovic et al., 2000; Klein et al., 2001; Hardin and Batey, 2004). KT BC1 belongs to a subtype of the classic KT that is exemplified by KT-58 in 23S rRNA. MBP, CaMKIIα, and PKMζ mRNA contain in their respective 3′ UTRs classic KT motifs that match consensus (Tiedge, 2006). R, purine; N, any nucleotide; blue, canonical G-C pairs of the C-stem; red, noncanonical G·A pairs of the NC-stem; orange, nominally unpaired internal loop nucleotides, may engage in stacking and trans–Sugar-Edge/Sugar-Edge interactions; yellow, extruded nucleotide. Motifs are aligned with their C-stems (blue, G-C pairs) to the left, NC-stems (red, G·A pairs) to the right of the asymmetric internal loop. In the consensus KT, the transitional position between the NC-stem and the resumption of A-form helical structure by G-C base pairs (referred to as N·N) may be occupied by an intervening base pair, by an unpaired residue, or not at all. KTs in small untranslated RNAs often carry a G·U wobble pair in this position (Rozhdestvensky et al., 2003; Hamma and Ferré-D'Amaré, 2004), although a sheared (trans–Hoogsteen/Sugar Edge) G·U pair is also allowed (Lescoute et al., 2005). Flanking G-C base pairs may occur in either the G-C or the C-G orientation. In the KT-58 subtype (including KT BC1), internal loop G and C nucleotides may also be part of an extended C-stem (Lescoute et al., 2005) and can therefore be rendered in either color coding.
© Copyright Policy
Related In: Results  -  Collection

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

fig9: The BC1 KT motif (KT BC1). Two general classes of KT motifs have been described, the classic KT and the minimal KT (Vidovic et al., 2000; Klein et al., 2001; Hardin and Batey, 2004). KT BC1 belongs to a subtype of the classic KT that is exemplified by KT-58 in 23S rRNA. MBP, CaMKIIα, and PKMζ mRNA contain in their respective 3′ UTRs classic KT motifs that match consensus (Tiedge, 2006). R, purine; N, any nucleotide; blue, canonical G-C pairs of the C-stem; red, noncanonical G·A pairs of the NC-stem; orange, nominally unpaired internal loop nucleotides, may engage in stacking and trans–Sugar-Edge/Sugar-Edge interactions; yellow, extruded nucleotide. Motifs are aligned with their C-stems (blue, G-C pairs) to the left, NC-stems (red, G·A pairs) to the right of the asymmetric internal loop. In the consensus KT, the transitional position between the NC-stem and the resumption of A-form helical structure by G-C base pairs (referred to as N·N) may be occupied by an intervening base pair, by an unpaired residue, or not at all. KTs in small untranslated RNAs often carry a G·U wobble pair in this position (Rozhdestvensky et al., 2003; Hamma and Ferré-D'Amaré, 2004), although a sheared (trans–Hoogsteen/Sugar Edge) G·U pair is also allowed (Lescoute et al., 2005). Flanking G-C base pairs may occur in either the G-C or the C-G orientation. In the KT-58 subtype (including KT BC1), internal loop G and C nucleotides may also be part of an extended C-stem (Lescoute et al., 2005) and can therefore be rendered in either color coding.
Mentions: Our data suggest that the KT BC1, which is located in the apical 5′ BC1 domain, serves as a long-range targeting code. A search algorithm (see Materials and methods) identified similar KT motifs in the DTEs of several targeted neural RNAs (see Discussion). Therefore, we hypothesized that a trans-acting factor (i.e., a decoding protein) that recognizes such KT motifs would interact with those RNAs that use them as spatial codes. One of the KT motifs identified by our search algorithm is located in the 3′ UTR of myelin basic protein (MBP) mRNA, an mRNA that is distally targeted in oligodendrocytes and neurons (Ainger et al., 1993; Shan et al., 2003). This KT MBP motif (Fig. 9) overlaps with a previously described 21-nt element in the MBP 3′ UTR that was initially recognized as an RNA transport signal (Ainger et al., 1997). It was later identified as a targeting-determinant response element for hnRNP A2 (A2RE; Hoek et al., 1998; Munro et al., 1999; Shan et al., 2000, 2003). We therefore reasoned that hnRNP A2 may also interact with 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