한빛사논문
- 조회1,857
Jong-Sun Lee1, Joshua T. Mendell1,2,3,4,5,*
1 Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA
2 Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
3 Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
4 Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
*Corresponding author : Joshua T. Mendell
Abstract
Antisense oligonucleotides (ASOs) that trigger RNase-H-mediated cleavage are commonly used to knock down transcripts for experimental or therapeutic purposes. In particular, ASOs are frequently used to functionally interrogate long noncoding RNAs (lncRNAs) and discriminate lncRNA loci that produce functional RNAs from those whose activity is attributable to the act of transcription. Transcription termination is triggered by cleavage of nascent transcripts, generally during polyadenylation, resulting in degradation of the residual RNA polymerase II (Pol II)-associated RNA by XRN2 and dissociation of elongating Pol II. Here, we show that ASOs act upon nascent transcripts and, consequently, induce premature transcription termination downstream of the cleavage site in an XRN2-dependent manner. Targeting the transcript 3′ end with ASOs, however, allows transcript knockdown while preserving Pol II association with the gene body. These results demonstrate that the effects of ASOs on transcription must be considered for appropriate experimental and therapeutic use of these reagents.
Keywords : antisense oligonucleotide; ASO; transcription termination; torpedo mechanism; long noncoding RNA; lncRNA; XRN2
논문정보
- Research article
- 2020년 01월 (BRIC 등록일 2020-01-15)
- 국외 연구진
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