Synthetic oligonucleotides recruit ILF2/3 to RNA transcripts to modulate splicing

Rigo, F., Hua, Y. M., Chun, S. J., Prakash, T. P., Krainer, A. R., Bennett, C. F. (June 2012) Synthetic oligonucleotides recruit ILF2/3 to RNA transcripts to modulate splicing. Nature Chemical Biology, 8 (6). pp. 555-561. ISSN 1552-4450

URL: http://www.ncbi.nlm.nih.gov/pubmed/22504300
DOI: 10.1038/nchembio.939

Abstract

We describe a new technology for recruiting specific proteins to RNA through selective recognition of heteroduplexes formed with chemically modified antisense oligonucleotides (ASOs). Typically, ASOs function by hybridizing to their RNA targets and blocking the binding of single-stranded RNA-binding proteins. Unexpectedly, we found that ASOs with 2'-deoxy-2'-fluoro (2'-F) nucleotides, but not with other 2' chemical modifications, have an additional property: they form heteroduplexes with RNA that are specifically recognized by the interleukin enhancer-binding factor 2 and 3 complex (ILF2/3). 2'-F ASO-directed recruitment of ILF2/3 to RNA can be harnessed to control gene expression by modulating alternative splicing of target transcripts. ILF2/3 recruitment to precursor mRNA near an exon results in omission of the exon from the mature mRNA, both in cell culture and in mice. We discuss the possibility of using chemically engineered ASOs that recruit specific proteins to modulate gene expression for therapeutic intervention.

Item Type: Paper
Uncontrolled Keywords: spinal muscular-atrophy single-stranded rna locked nucleic-acid binding proteins antisense oligonucleotides pyruvate-kinase high-affinity gene disease therapeutics
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNA regulation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > oligonucleotide
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNA splicing
CSHL Authors:
Communities: CSHL labs > Krainer lab
CSHL Cancer Center Program > Gene Regulation and Cell Proliferation
Depositing User: Matt Covey
Date: June 2012
Date Deposited: 30 Jan 2013 14:36
Last Modified: 13 Oct 2015 19:02
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27028

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