Enhanced CLIP Uncovers IMP Protein-RNA Targets in Human Pluripotent Stem Cells Important for Cell Adhesion and Survival.

TitleEnhanced CLIP Uncovers IMP Protein-RNA Targets in Human Pluripotent Stem Cells Important for Cell Adhesion and Survival.
Publication TypeJournal Article
Year of Publication2016
AuthorsConway AE, Van Nostrand EL, Pratt GA, Aigner S, Wilbert ML, Sundararaman B, Freese P, Lambert NJ, Sathe S, Liang TY, Essex A, Landais S, Burge CB, D Jones L, Yeo GW
JournalCell Rep
Volume15
Issue3
Pagination666-79
Date Published2016 Apr 19
ISSN2211-1247
Abstract

Human pluripotent stem cells (hPSCs) require precise control of post-transcriptional RNA networks to maintain proliferation and survival. Using enhanced UV crosslinking and immunoprecipitation (eCLIP), we identify RNA targets of the IMP/IGF2BP family of RNA-binding proteins in hPSCs. At the broad region and binding site levels, IMP1 and IMP2 show reproducible binding to a large and overlapping set of 3' UTR-enriched targets. RNA Bind-N-seq applied to recombinant full-length IMP1 and IMP2 reveals CA-rich motifs that are enriched in eCLIP-defined binding sites. We observe that IMP1 loss in hPSCs recapitulates IMP1 phenotypes, including a reduction in cell adhesion and increase in cell death. For cell adhesion, we find IMP1 maintains levels of integrin mRNA specifically regulating RNA stability of ITGB5 in hPSCs. Additionally, we show that IMP1 can be linked to hPSC survival via direct target BCL2. Thus, transcriptome-wide binding profiles identify hPSC targets modulating well-characterized IMP1 roles.

DOI10.1016/j.celrep.2016.03.052
PubMed URLhttp://www.ncbi.nlm.nih.gov/pubmed/27068461?dopt=Abstract
Alternate JournalCell Rep
PubMed ID27068461
PubMed Central IDPMC4839292
Grant ListR01 HG004659 / HG / NHGRI NIH HHS / United States
R01 NS075449 / NS / NINDS NIH HHS / United States
Track(s): 
Bioinformatics and Systems Biology