Buckley PT, Lee MT, Sul JY, Miyashiro KY, Bell TJ, Fisher SA, Kim J, Eberwine J.
Cytoplasmic intron sequence-retaining transcripts can be dendritically targeted via ID element retrotransposons.
Neuron. 2011 Mar 10;69(5):877-84.
PubMed.
This article in Neuron published by Buckley et al. describes findings in explanted and cultured neurons (ex vivo) that intron-retained, repetitive sequences, so-called identifier elements (ID elements), confer dendritic targeting competence to neuronal transcripts, partially in agreement with previous ex-vivo findings by Muslimov et al. (Muslimov et al., 1997). However, the in-vivo findings by our group using transgenic mouse models do not support the idea that ID elements could act as dendritic targeting elements for mRNAs (Khanam et al., 2007). The authors have claimed that the position of the ID elements in a transcript is crucial for such a phenomenon, and that the location of the ID elements in 3’ UTR is not ideal. This is quite intriguing, as most of the dendritc targeting elements identified so far are located in 3’ UTRs.
It is noteworthy that ID elements are restricted to the mammalian order of rodentia (rodents). The question of whether a similar mechanism, if it exists at all, is in place in primates, including humans, is difficult to address.
Transposed elements, including short interspersed elements (SINEs), have the potential to impart novel functions to existing genes including regulatory elements or novel exons (Brosius, 1991). Splice variants can have altered localization and/or expression and functional consequence. Splice variants are presumably one of the many potential causes in genetic disease, possibly including Alzheimer’s and Parkinson’s disease. On the other hand, it is not clear if the relevant mRNAs (APP and tau) are transported into dendrites, as the RNA localization data in the Allen Human Brain Atlas do not reveal dendritic staining.
While the idea is interesting that the intron retained sequences impart dendritic targeting competence, the data presented do not fully support the hypothesis. For example, experimental evidence is lacking to show that deletion of ID elements would render the transcripts non-dendritic. If the hypothesis is correct, then it would raise the question as to how dendritic transport and its regulation is achieved in non-rodent species, where clearly it must also occur for a functional mammalian nervous system. There is no evidence so far that the 5’ Alu domain retrosposon found in the human BC200 gene has any role in the transport of BC200 RNA.
References:
Muslimov IA, Santi E, Homel P, Perini S, Higgins D, Tiedge H.
RNA transport in dendrites: a cis-acting targeting element is contained within neuronal BC1 RNA.
J Neurosci. 1997 Jun 15;17(12):4722-33.
PubMed.
Khanam T, Raabe CA, Kiefmann M, Handel S, Skryabin BV, Brosius J.
Can ID repetitive elements serve as cis-acting dendritic targeting elements? An in vivo study.
PLoS One. 2007;2(9):e961.
PubMed.
Brosius J.
Retroposons--seeds of evolution.
Science. 1991 Feb 15;251(4995):753.
PubMed.
Comments
University of Münster
This article in Neuron published by Buckley et al. describes findings in explanted and cultured neurons (ex vivo) that intron-retained, repetitive sequences, so-called identifier elements (ID elements), confer dendritic targeting competence to neuronal transcripts, partially in agreement with previous ex-vivo findings by Muslimov et al. (Muslimov et al., 1997). However, the in-vivo findings by our group using transgenic mouse models do not support the idea that ID elements could act as dendritic targeting elements for mRNAs (Khanam et al., 2007). The authors have claimed that the position of the ID elements in a transcript is crucial for such a phenomenon, and that the location of the ID elements in 3’ UTR is not ideal. This is quite intriguing, as most of the dendritc targeting elements identified so far are located in 3’ UTRs.
It is noteworthy that ID elements are restricted to the mammalian order of rodentia (rodents). The question of whether a similar mechanism, if it exists at all, is in place in primates, including humans, is difficult to address.
Transposed elements, including short interspersed elements (SINEs), have the potential to impart novel functions to existing genes including regulatory elements or novel exons (Brosius, 1991). Splice variants can have altered localization and/or expression and functional consequence. Splice variants are presumably one of the many potential causes in genetic disease, possibly including Alzheimer’s and Parkinson’s disease. On the other hand, it is not clear if the relevant mRNAs (APP and tau) are transported into dendrites, as the RNA localization data in the Allen Human Brain Atlas do not reveal dendritic staining.
While the idea is interesting that the intron retained sequences impart dendritic targeting competence, the data presented do not fully support the hypothesis. For example, experimental evidence is lacking to show that deletion of ID elements would render the transcripts non-dendritic. If the hypothesis is correct, then it would raise the question as to how dendritic transport and its regulation is achieved in non-rodent species, where clearly it must also occur for a functional mammalian nervous system. There is no evidence so far that the 5’ Alu domain retrosposon found in the human BC200 gene has any role in the transport of BC200 RNA.
References:
Muslimov IA, Santi E, Homel P, Perini S, Higgins D, Tiedge H. RNA transport in dendrites: a cis-acting targeting element is contained within neuronal BC1 RNA. J Neurosci. 1997 Jun 15;17(12):4722-33. PubMed.
Khanam T, Raabe CA, Kiefmann M, Handel S, Skryabin BV, Brosius J. Can ID repetitive elements serve as cis-acting dendritic targeting elements? An in vivo study. PLoS One. 2007;2(9):e961. PubMed.
Brosius J. Retroposons--seeds of evolution. Science. 1991 Feb 15;251(4995):753. PubMed.
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