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U1 adaptors result in reduction of multiple pre-mRNA species principally by sequestering U1snRNP.

ABSTRACT: U1 Adaptors are a recently reported novel approach for targeted reduction of mRNA transcripts. A U1 adaptor oligonucleotide comprising of a target-complimentary hybridization domain and a U1 recruitment domain, directs the U1 snRNP complex to the terminal exon of a targeted gene, subsequently inhibiting poly(A) tail addition and leading to degradation of that RNA species within the nucleus. Here, we present data demonstrating U1 adapter-mediated gene silencing can result in significant 'off-target' silencing effects as demonstrated by the reduction of multiple mRNA species that were not intended to be targeted. Our data suggest that a substantial portion of this U1 adaptor-mediated off-target mRNA reduction is the result of sequestration U1 snRNP at levels sufficient to affect splicing and processing of non-target transcripts.

SUBMITTER: Vickers TA 

PROVIDER: S-EPMC3105408 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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U1 adaptors result in reduction of multiple pre-mRNA species principally by sequestering U1snRNP.

Vickers Timothy A TA   Sabripour Mahyar M   Crooke Stanley T ST  

Nucleic acids research 20110316 10

U1 Adaptors are a recently reported novel approach for targeted reduction of mRNA transcripts. A U1 adaptor oligonucleotide comprising of a target-complimentary hybridization domain and a U1 recruitment domain, directs the U1 snRNP complex to the terminal exon of a targeted gene, subsequently inhibiting poly(A) tail addition and leading to degradation of that RNA species within the nucleus. Here, we present data demonstrating U1 adapter-mediated gene silencing can result in significant 'off-targ  ...[more]