論文

査読有り 国際誌
2020年12月

Processing of Alu small RNAs by DICER/ADAR1 complexes and their RNAi targets

RNA
  • Yusuke Shiromoto
  • ,
  • Masayuki Sakurai
  • ,
  • Helen Qu
  • ,
  • Andrew V. Kossenkov
  • ,
  • Kazuko Nishikura

26
12
開始ページ
1801
終了ページ
1814
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1261/rna.076745.120
出版者・発行元
Cold Spring Harbor Laboratory

In addition to adenosine-to-inosine RNA editing activities, ADAR1 has been shown to have various RNA editing-independent activities including modulation of RNAi efficacy. We previously reported that ADAR1 forms a heterodimer complex with DICER and facilitates processing of pre-miRNAs to mature miRNAs. In addition to miRNA synthesis, DICER is involved in processing of long dsRNAs into small RNAs (endo-siRNAs). Generation of retrotransposon-derived endo-siRNAs by DICER and their functions in regulation of transcripts in mouse oocytes has been previously reported. However, the synthesis and functions of endo-siRNAs in somatic cells remain largely unknown. Here, we report that ADAR1 together with DICER generates endogenous small RNAs, Alu endo-siRNAs by cleaving long double-stranded regions of inverted Alu repeats. We identified AGO2-loaded Alu endo-siRNAs, which are highly expressed in commonly used cell lines. These Alu endo-siRNAs carrying both sense and antisense Alu sequences seem to target a set of genes containing a single Alu sequence, either antisense or sense, respectively, within their 3'UTR. In silico screening identified potential RNA silencing target genes for these Alu endo-siRNAs. We present results of a proof-of-concept experiment, in which sense Alu endo-siRNAs derived from AluSz and AluJr family elements target CUB Domain Containing Protein 1 mRNAs containing an antisense copy of AluJb in their 3'UTRs and consequently induce apoptosis in HeLa cells. Our results clearly indicate that Alu endo-siRNAs are functional also in somatic cells.

リンク情報
DOI
https://doi.org/10.1261/rna.076745.120
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32817447
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668262
URL
https://syndication.highwire.org/content/doi/10.1261/rna.076745.120
ID情報
  • DOI : 10.1261/rna.076745.120
  • ISSN : 1355-8382
  • eISSN : 1469-9001
  • PubMed ID : 32817447
  • PubMed Central 記事ID : PMC7668262

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