Cargando…
Genome-wide analysis of YB-1-RNA interactions reveals a novel role of YB-1 in miRNA processing in glioblastoma multiforme
Altered miRNA expression is believed to play a crucial role in a variety of human cancers; however, the mechanisms leading to the dysregulation of miRNA expression remain elusive. In this study, we report that the human Y box-binding protein (YB-1), a major mRNA packaging protein, is a novel modulat...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4787835/ https://www.ncbi.nlm.nih.gov/pubmed/26240386 http://dx.doi.org/10.1093/nar/gkv779 |
_version_ | 1782420698653786112 |
---|---|
author | Wu, Shuai-Lai Fu, Xing Huang, Jinyan Jia, Ting-Ting Zong, Feng-Yang Mu, Shi-Rong Zhu, Hong Yan, Yong Qiu, Shuwei Wu, Qun Yan, Wei Peng, Ying Chen, Juxiang Hui, Jingyi |
author_facet | Wu, Shuai-Lai Fu, Xing Huang, Jinyan Jia, Ting-Ting Zong, Feng-Yang Mu, Shi-Rong Zhu, Hong Yan, Yong Qiu, Shuwei Wu, Qun Yan, Wei Peng, Ying Chen, Juxiang Hui, Jingyi |
author_sort | Wu, Shuai-Lai |
collection | PubMed |
description | Altered miRNA expression is believed to play a crucial role in a variety of human cancers; however, the mechanisms leading to the dysregulation of miRNA expression remain elusive. In this study, we report that the human Y box-binding protein (YB-1), a major mRNA packaging protein, is a novel modulator of miRNA processing in glioblastoma multiforme (GBM). Using individual nucleotide-resolution crosslinking immunoprecipitation coupled to deep sequencing (iCLIP-seq), we performed the first genome-wide analysis of the in vivo YB-1-RNA interactions and found that YB-1 preferentially recognizes a UYAUC consensus motif and binds to the majority of coding gene transcripts including pre-mRNAs and mature mRNAs. Remarkably, our data show that YB-1 also binds extensively to the terminal loop region of pri-/pre-miR-29b-2 and regulates the biogenesis of miR-29b-2 by blocking the recruitment of microprocessor and Dicer to its precursors. Furthermore, we show that down-regulation of miR-29b by YB-1, which is up-regulated in GBM, is important for cell proliferation. Together, our findings reveal a novel function of YB-1 in regulating non-coding RNA expression, which has important implications in tumorigenesis. |
format | Online Article Text |
id | pubmed-4787835 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-47878352016-03-14 Genome-wide analysis of YB-1-RNA interactions reveals a novel role of YB-1 in miRNA processing in glioblastoma multiforme Wu, Shuai-Lai Fu, Xing Huang, Jinyan Jia, Ting-Ting Zong, Feng-Yang Mu, Shi-Rong Zhu, Hong Yan, Yong Qiu, Shuwei Wu, Qun Yan, Wei Peng, Ying Chen, Juxiang Hui, Jingyi Nucleic Acids Res RNA Altered miRNA expression is believed to play a crucial role in a variety of human cancers; however, the mechanisms leading to the dysregulation of miRNA expression remain elusive. In this study, we report that the human Y box-binding protein (YB-1), a major mRNA packaging protein, is a novel modulator of miRNA processing in glioblastoma multiforme (GBM). Using individual nucleotide-resolution crosslinking immunoprecipitation coupled to deep sequencing (iCLIP-seq), we performed the first genome-wide analysis of the in vivo YB-1-RNA interactions and found that YB-1 preferentially recognizes a UYAUC consensus motif and binds to the majority of coding gene transcripts including pre-mRNAs and mature mRNAs. Remarkably, our data show that YB-1 also binds extensively to the terminal loop region of pri-/pre-miR-29b-2 and regulates the biogenesis of miR-29b-2 by blocking the recruitment of microprocessor and Dicer to its precursors. Furthermore, we show that down-regulation of miR-29b by YB-1, which is up-regulated in GBM, is important for cell proliferation. Together, our findings reveal a novel function of YB-1 in regulating non-coding RNA expression, which has important implications in tumorigenesis. Oxford University Press 2015-09-30 2015-08-03 /pmc/articles/PMC4787835/ /pubmed/26240386 http://dx.doi.org/10.1093/nar/gkv779 Text en © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | RNA Wu, Shuai-Lai Fu, Xing Huang, Jinyan Jia, Ting-Ting Zong, Feng-Yang Mu, Shi-Rong Zhu, Hong Yan, Yong Qiu, Shuwei Wu, Qun Yan, Wei Peng, Ying Chen, Juxiang Hui, Jingyi Genome-wide analysis of YB-1-RNA interactions reveals a novel role of YB-1 in miRNA processing in glioblastoma multiforme |
title | Genome-wide analysis of YB-1-RNA interactions reveals a novel role of YB-1 in miRNA processing in glioblastoma multiforme |
title_full | Genome-wide analysis of YB-1-RNA interactions reveals a novel role of YB-1 in miRNA processing in glioblastoma multiforme |
title_fullStr | Genome-wide analysis of YB-1-RNA interactions reveals a novel role of YB-1 in miRNA processing in glioblastoma multiforme |
title_full_unstemmed | Genome-wide analysis of YB-1-RNA interactions reveals a novel role of YB-1 in miRNA processing in glioblastoma multiforme |
title_short | Genome-wide analysis of YB-1-RNA interactions reveals a novel role of YB-1 in miRNA processing in glioblastoma multiforme |
title_sort | genome-wide analysis of yb-1-rna interactions reveals a novel role of yb-1 in mirna processing in glioblastoma multiforme |
topic | RNA |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4787835/ https://www.ncbi.nlm.nih.gov/pubmed/26240386 http://dx.doi.org/10.1093/nar/gkv779 |
work_keys_str_mv | AT wushuailai genomewideanalysisofyb1rnainteractionsrevealsanovelroleofyb1inmirnaprocessinginglioblastomamultiforme AT fuxing genomewideanalysisofyb1rnainteractionsrevealsanovelroleofyb1inmirnaprocessinginglioblastomamultiforme AT huangjinyan genomewideanalysisofyb1rnainteractionsrevealsanovelroleofyb1inmirnaprocessinginglioblastomamultiforme AT jiatingting genomewideanalysisofyb1rnainteractionsrevealsanovelroleofyb1inmirnaprocessinginglioblastomamultiforme AT zongfengyang genomewideanalysisofyb1rnainteractionsrevealsanovelroleofyb1inmirnaprocessinginglioblastomamultiforme AT mushirong genomewideanalysisofyb1rnainteractionsrevealsanovelroleofyb1inmirnaprocessinginglioblastomamultiforme AT zhuhong genomewideanalysisofyb1rnainteractionsrevealsanovelroleofyb1inmirnaprocessinginglioblastomamultiforme AT yanyong genomewideanalysisofyb1rnainteractionsrevealsanovelroleofyb1inmirnaprocessinginglioblastomamultiforme AT qiushuwei genomewideanalysisofyb1rnainteractionsrevealsanovelroleofyb1inmirnaprocessinginglioblastomamultiforme AT wuqun genomewideanalysisofyb1rnainteractionsrevealsanovelroleofyb1inmirnaprocessinginglioblastomamultiforme AT yanwei genomewideanalysisofyb1rnainteractionsrevealsanovelroleofyb1inmirnaprocessinginglioblastomamultiforme AT pengying genomewideanalysisofyb1rnainteractionsrevealsanovelroleofyb1inmirnaprocessinginglioblastomamultiforme AT chenjuxiang genomewideanalysisofyb1rnainteractionsrevealsanovelroleofyb1inmirnaprocessinginglioblastomamultiforme AT huijingyi genomewideanalysisofyb1rnainteractionsrevealsanovelroleofyb1inmirnaprocessinginglioblastomamultiforme |