Dual REST-dependence of L1CAM: from gene expression to alternative splicing governed by Nova2 in neural cells
2012
Authors
Mikulak, JoannaNegrini, Sara
Lazić, Andrijana
D'Alessandro, Rosalba
Mavilio, Domenico
Meldolesi, Jacopo
Article (Published version)
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L1 cell adhesion molecule (L1CAM), an adhesion/signaling protein encoded by a gene target of the transcription repressor RE-1-Silencing Transcription factor (REST), is expressed in two alternatively spliced isoforms. The full-length isoform, typical of low-REST neural cells, plays key roles in survival/migration, outgrowth/fasciculation/regeneration of axons, synaptic plasticity; the isoform missing two mini-exons, abundant in a few high-REST non-neural cells, maintains some effect on migration and proliferation. To investigate whether and how L1CAM alternative splicing depends on REST we used neural cell models expressing low or high levels of REST (PC12, SH-SY5Y, differentiated NT2/D1 and primary neurons transduced or not with REST). The short isoform was found to rise when the low-REST levels of neural cells were experimentally increased, while the full-length isoform increased in high-REST cells when the repressor tone was attenuated. These results were due to Nova2, a neural cell-...specific splicing factor shown here to be repressed by REST. REST control of L1CAM occurs therefore by two mechanisms, transcription and alternative splicing. The splicing mechanism, affecting not only L1CAM but all Nova2 targets (similar to 7% of brain-specific splicing, including the mRNAs of other adhesion and synaptic proteins) is expected to be critical during development and important also for the structure and function of mature neural cells.
Keywords:
transduction / transcription / ss-catenin / REST transfection / primary neurons / PC12 cells / NT2 / D1 cellsSource:
Journal of Neurochemistry, 2012, 120, 5, 699-709Publisher:
- Wiley, Hoboken
Funding / projects:
- Telethon [GGGP09066]
- European Union
- Italian Ministry of Health [FP7-People-2009-IRG 249249, RF-ICH-2009-1304134]
- Studying signal transduction pathways and epigenetic mechanisms that control human SOX genes expression: further insight into their roles in cell fate determination and differentiation (RS-MESTD-Basic Research (BR or ON)-173051)
- Izučavanje regulacije ekspresije i funkcije humanih SOX gena (RS-MESTD-MPN2006-2010-143028)
DOI: 10.1111/j.1471-4159.2011.07626.x
ISSN: 0022-3042
PubMed: 22176577
WoS: 000300503400006
Scopus: 2-s2.0-84857194091
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Institution/Community
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Mikulak, Joanna AU - Negrini, Sara AU - Lazić, Andrijana AU - D'Alessandro, Rosalba AU - Mavilio, Domenico AU - Meldolesi, Jacopo PY - 2012 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/581 AB - L1 cell adhesion molecule (L1CAM), an adhesion/signaling protein encoded by a gene target of the transcription repressor RE-1-Silencing Transcription factor (REST), is expressed in two alternatively spliced isoforms. The full-length isoform, typical of low-REST neural cells, plays key roles in survival/migration, outgrowth/fasciculation/regeneration of axons, synaptic plasticity; the isoform missing two mini-exons, abundant in a few high-REST non-neural cells, maintains some effect on migration and proliferation. To investigate whether and how L1CAM alternative splicing depends on REST we used neural cell models expressing low or high levels of REST (PC12, SH-SY5Y, differentiated NT2/D1 and primary neurons transduced or not with REST). The short isoform was found to rise when the low-REST levels of neural cells were experimentally increased, while the full-length isoform increased in high-REST cells when the repressor tone was attenuated. These results were due to Nova2, a neural cell-specific splicing factor shown here to be repressed by REST. REST control of L1CAM occurs therefore by two mechanisms, transcription and alternative splicing. The splicing mechanism, affecting not only L1CAM but all Nova2 targets (similar to 7% of brain-specific splicing, including the mRNAs of other adhesion and synaptic proteins) is expected to be critical during development and important also for the structure and function of mature neural cells. PB - Wiley, Hoboken T2 - Journal of Neurochemistry T1 - Dual REST-dependence of L1CAM: from gene expression to alternative splicing governed by Nova2 in neural cells EP - 709 IS - 5 SP - 699 VL - 120 DO - 10.1111/j.1471-4159.2011.07626.x ER -
@article{ author = "Mikulak, Joanna and Negrini, Sara and Lazić, Andrijana and D'Alessandro, Rosalba and Mavilio, Domenico and Meldolesi, Jacopo", year = "2012", abstract = "L1 cell adhesion molecule (L1CAM), an adhesion/signaling protein encoded by a gene target of the transcription repressor RE-1-Silencing Transcription factor (REST), is expressed in two alternatively spliced isoforms. The full-length isoform, typical of low-REST neural cells, plays key roles in survival/migration, outgrowth/fasciculation/regeneration of axons, synaptic plasticity; the isoform missing two mini-exons, abundant in a few high-REST non-neural cells, maintains some effect on migration and proliferation. To investigate whether and how L1CAM alternative splicing depends on REST we used neural cell models expressing low or high levels of REST (PC12, SH-SY5Y, differentiated NT2/D1 and primary neurons transduced or not with REST). The short isoform was found to rise when the low-REST levels of neural cells were experimentally increased, while the full-length isoform increased in high-REST cells when the repressor tone was attenuated. These results were due to Nova2, a neural cell-specific splicing factor shown here to be repressed by REST. REST control of L1CAM occurs therefore by two mechanisms, transcription and alternative splicing. The splicing mechanism, affecting not only L1CAM but all Nova2 targets (similar to 7% of brain-specific splicing, including the mRNAs of other adhesion and synaptic proteins) is expected to be critical during development and important also for the structure and function of mature neural cells.", publisher = "Wiley, Hoboken", journal = "Journal of Neurochemistry", title = "Dual REST-dependence of L1CAM: from gene expression to alternative splicing governed by Nova2 in neural cells", pages = "709-699", number = "5", volume = "120", doi = "10.1111/j.1471-4159.2011.07626.x" }
Mikulak, J., Negrini, S., Lazić, A., D'Alessandro, R., Mavilio, D.,& Meldolesi, J.. (2012). Dual REST-dependence of L1CAM: from gene expression to alternative splicing governed by Nova2 in neural cells. in Journal of Neurochemistry Wiley, Hoboken., 120(5), 699-709. https://doi.org/10.1111/j.1471-4159.2011.07626.x
Mikulak J, Negrini S, Lazić A, D'Alessandro R, Mavilio D, Meldolesi J. Dual REST-dependence of L1CAM: from gene expression to alternative splicing governed by Nova2 in neural cells. in Journal of Neurochemistry. 2012;120(5):699-709. doi:10.1111/j.1471-4159.2011.07626.x .
Mikulak, Joanna, Negrini, Sara, Lazić, Andrijana, D'Alessandro, Rosalba, Mavilio, Domenico, Meldolesi, Jacopo, "Dual REST-dependence of L1CAM: from gene expression to alternative splicing governed by Nova2 in neural cells" in Journal of Neurochemistry, 120, no. 5 (2012):699-709, https://doi.org/10.1111/j.1471-4159.2011.07626.x . .