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Detection of the LINE-1 retrotransposon RNA-binding protein ORF1p in different anatomical regions of the human brain

BACKGROUND: Recent reports indicate that retrotransposons – a type of mobile DNA – can contribute to neuronal genetic diversity in mammals. Retrotransposons are genetic elements that mobilize via an RNA intermediate by a “copy-and-paste” mechanism termed retrotransposition. Long Interspersed Element...

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Autores principales: Sur, Debpali, Kustwar, Raj Kishor, Budania, Savita, Mahadevan, Anita, Hancks, Dustin C., Yadav, Vijay, Shankar, S. K., Mandal, Prabhat K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5700708/
https://www.ncbi.nlm.nih.gov/pubmed/29201157
http://dx.doi.org/10.1186/s13100-017-0101-4
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author Sur, Debpali
Kustwar, Raj Kishor
Budania, Savita
Mahadevan, Anita
Hancks, Dustin C.
Yadav, Vijay
Shankar, S. K.
Mandal, Prabhat K.
author_facet Sur, Debpali
Kustwar, Raj Kishor
Budania, Savita
Mahadevan, Anita
Hancks, Dustin C.
Yadav, Vijay
Shankar, S. K.
Mandal, Prabhat K.
author_sort Sur, Debpali
collection PubMed
description BACKGROUND: Recent reports indicate that retrotransposons – a type of mobile DNA – can contribute to neuronal genetic diversity in mammals. Retrotransposons are genetic elements that mobilize via an RNA intermediate by a “copy-and-paste” mechanism termed retrotransposition. Long Interspersed Element-1 (LINE-1 or L1) is the only active autonomous retrotransposon in humans and its activity is responsible for ~ 30% of genomic mass. Historically, L1 retrotransposition was thought to be restricted to the germline; however, new data indicate L1 s are active in somatic tissue with certain regions of the brain being highly permissive. The functional implications of L1 insertional activity in the brain and how host cells regulate it are incomplete. While deep sequencing and qPCR analysis have shown that L1 copy number is much higher in certain parts of the human brain, direct in vivo studies regarding detection of L1-encoded proteins is lacking due to ineffective reagents. RESULTS: Using a polyclonal antibody we generated against the RNA-binding (RRM) domain of L1 ORF1p, we observe widespread ORF1p expression in post-mortem human brain samples including the hippocampus which has known elevated rates of retrotransposition. In addition, we find that two brains from different individuals of different ages display very different expression of ORF1p, especially in the frontal cortex. CONCLUSIONS: We hypothesize that discordance of ORF1p expression in parts of the brain reported to display elevated levels of retrotransposition may suggest the existence of factors mediating post-translational regulation of L1 activity in the human brain. Furthermore, this antibody reagent will be useful as a complementary means to confirm findings related to retrotransposon biology and activity in the brain and other tissues in vivo. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13100-017-0101-4) contains supplementary material, which is available to authorized users.
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spelling pubmed-57007082017-12-01 Detection of the LINE-1 retrotransposon RNA-binding protein ORF1p in different anatomical regions of the human brain Sur, Debpali Kustwar, Raj Kishor Budania, Savita Mahadevan, Anita Hancks, Dustin C. Yadav, Vijay Shankar, S. K. Mandal, Prabhat K. Mob DNA Research BACKGROUND: Recent reports indicate that retrotransposons – a type of mobile DNA – can contribute to neuronal genetic diversity in mammals. Retrotransposons are genetic elements that mobilize via an RNA intermediate by a “copy-and-paste” mechanism termed retrotransposition. Long Interspersed Element-1 (LINE-1 or L1) is the only active autonomous retrotransposon in humans and its activity is responsible for ~ 30% of genomic mass. Historically, L1 retrotransposition was thought to be restricted to the germline; however, new data indicate L1 s are active in somatic tissue with certain regions of the brain being highly permissive. The functional implications of L1 insertional activity in the brain and how host cells regulate it are incomplete. While deep sequencing and qPCR analysis have shown that L1 copy number is much higher in certain parts of the human brain, direct in vivo studies regarding detection of L1-encoded proteins is lacking due to ineffective reagents. RESULTS: Using a polyclonal antibody we generated against the RNA-binding (RRM) domain of L1 ORF1p, we observe widespread ORF1p expression in post-mortem human brain samples including the hippocampus which has known elevated rates of retrotransposition. In addition, we find that two brains from different individuals of different ages display very different expression of ORF1p, especially in the frontal cortex. CONCLUSIONS: We hypothesize that discordance of ORF1p expression in parts of the brain reported to display elevated levels of retrotransposition may suggest the existence of factors mediating post-translational regulation of L1 activity in the human brain. Furthermore, this antibody reagent will be useful as a complementary means to confirm findings related to retrotransposon biology and activity in the brain and other tissues in vivo. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13100-017-0101-4) contains supplementary material, which is available to authorized users. BioMed Central 2017-11-22 /pmc/articles/PMC5700708/ /pubmed/29201157 http://dx.doi.org/10.1186/s13100-017-0101-4 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Sur, Debpali
Kustwar, Raj Kishor
Budania, Savita
Mahadevan, Anita
Hancks, Dustin C.
Yadav, Vijay
Shankar, S. K.
Mandal, Prabhat K.
Detection of the LINE-1 retrotransposon RNA-binding protein ORF1p in different anatomical regions of the human brain
title Detection of the LINE-1 retrotransposon RNA-binding protein ORF1p in different anatomical regions of the human brain
title_full Detection of the LINE-1 retrotransposon RNA-binding protein ORF1p in different anatomical regions of the human brain
title_fullStr Detection of the LINE-1 retrotransposon RNA-binding protein ORF1p in different anatomical regions of the human brain
title_full_unstemmed Detection of the LINE-1 retrotransposon RNA-binding protein ORF1p in different anatomical regions of the human brain
title_short Detection of the LINE-1 retrotransposon RNA-binding protein ORF1p in different anatomical regions of the human brain
title_sort detection of the line-1 retrotransposon rna-binding protein orf1p in different anatomical regions of the human brain
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5700708/
https://www.ncbi.nlm.nih.gov/pubmed/29201157
http://dx.doi.org/10.1186/s13100-017-0101-4
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