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LINE-2 transposable elements are a source of functional human microRNAs and target sites

Petri, Rebecca LU ; Brattås, Per Ludvik LU ; Sharma, Yogita LU ; Jönsson, Marie E. LU ; Pircs, Karolina LU ; Bengzon, Johan LU and Jakobsson, Johan LU (2019) In PLoS Genetics 15(3). p.1008036-1008036
Abstract

Transposable elements (TEs) are dynamically expressed at high levels in multiple human tissues, but the function of TE-derived transcripts remains largely unknown. In this study, we identify numerous TE-derived microRNAs (miRNAs) by conducting Argonaute2 RNA immunoprecipitation followed by small RNA sequencing (AGO2 RIP-seq) on human brain tissue. Many of these miRNAs originated from LINE-2 (L2) elements, which entered the human genome around 100-300 million years ago. L2-miRNAs derived from the 3' end of the L2 consensus sequence and thus shared very similar sequences, indicating that L2-miRNAs could target transcripts with L2s in their 3'UTR. In line with this, many protein-coding genes carried fragments of L2-derived sequences in... (More)

Transposable elements (TEs) are dynamically expressed at high levels in multiple human tissues, but the function of TE-derived transcripts remains largely unknown. In this study, we identify numerous TE-derived microRNAs (miRNAs) by conducting Argonaute2 RNA immunoprecipitation followed by small RNA sequencing (AGO2 RIP-seq) on human brain tissue. Many of these miRNAs originated from LINE-2 (L2) elements, which entered the human genome around 100-300 million years ago. L2-miRNAs derived from the 3' end of the L2 consensus sequence and thus shared very similar sequences, indicating that L2-miRNAs could target transcripts with L2s in their 3'UTR. In line with this, many protein-coding genes carried fragments of L2-derived sequences in their 3'UTR: these sequences served as target sites for L2-miRNAs. L2-miRNAs and their targets were generally ubiquitously expressed at low levels in multiple human tissues, suggesting a role for this network in buffering transcriptional levels of housekeeping genes. In addition, we also found evidence that this network is perturbed in glioblastoma. In summary, our findings uncover a TE-based post-transcriptional network that shapes transcriptional regulation in human cells.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS Genetics
volume
15
issue
3
pages
1008036 - 1008036
publisher
Public Library of Science
external identifiers
  • scopus:85063712282
ISSN
1553-7404
DOI
10.1371/journal.pgen.1008036
language
English
LU publication?
yes
id
ad159d99-2f7b-47a1-aa0f-d8a4b02b7fa1
date added to LUP
2019-04-10 10:57:33
date last changed
2019-09-08 04:38:34
@article{ad159d99-2f7b-47a1-aa0f-d8a4b02b7fa1,
  abstract     = {<p>Transposable elements (TEs) are dynamically expressed at high levels in multiple human tissues, but the function of TE-derived transcripts remains largely unknown. In this study, we identify numerous TE-derived microRNAs (miRNAs) by conducting Argonaute2 RNA immunoprecipitation followed by small RNA sequencing (AGO2 RIP-seq) on human brain tissue. Many of these miRNAs originated from LINE-2 (L2) elements, which entered the human genome around 100-300 million years ago. L2-miRNAs derived from the 3' end of the L2 consensus sequence and thus shared very similar sequences, indicating that L2-miRNAs could target transcripts with L2s in their 3'UTR. In line with this, many protein-coding genes carried fragments of L2-derived sequences in their 3'UTR: these sequences served as target sites for L2-miRNAs. L2-miRNAs and their targets were generally ubiquitously expressed at low levels in multiple human tissues, suggesting a role for this network in buffering transcriptional levels of housekeeping genes. In addition, we also found evidence that this network is perturbed in glioblastoma. In summary, our findings uncover a TE-based post-transcriptional network that shapes transcriptional regulation in human cells.</p>},
  author       = {Petri, Rebecca and Brattås, Per Ludvik and Sharma, Yogita and Jönsson, Marie E. and Pircs, Karolina and Bengzon, Johan and Jakobsson, Johan},
  issn         = {1553-7404},
  language     = {eng},
  number       = {3},
  pages        = {1008036--1008036},
  publisher    = {Public Library of Science},
  series       = {PLoS Genetics},
  title        = {LINE-2 transposable elements are a source of functional human microRNAs and target sites},
  url          = {http://dx.doi.org/10.1371/journal.pgen.1008036},
  volume       = {15},
  year         = {2019},
}