Identification of Abundant and Functional dodecaRNAs (doRNAs) Derived from Ribosomal RNA

Int J Mol Sci. 2021 Sep 9;22(18):9757. doi: 10.3390/ijms22189757.

Abstract

Using a modified RNA-sequencing (RNA-seq) approach, we discovered a new family of unusually short RNAs mapping to ribosomal RNA 5.8S, which we named dodecaRNAs (doRNAs), according to the number of core nucleotides (12 nt) their members contain. Using a new quantitative detection method that we developed, we confirmed our RNA-seq data and determined that the minimal core doRNA sequence and its 13-nt variant C-doRNA (doRNA with a 5' Cytosine) are the two most abundant doRNAs, which, together, may outnumber microRNAs. The C-doRNA/doRNA ratio is stable within species but differed between species. doRNA and C-doRNA are mainly cytoplasmic and interact with heterogeneous nuclear ribonucleoproteins (hnRNP) A0, A1 and A2B1, but not Argonaute 2. Reporter gene activity assays suggest that C-doRNA may function as a regulator of Annexin II receptor (AXIIR) expression. doRNAs are differentially expressed in prostate cancer cells/tissues and may control cell migration. These findings suggest that unusually short RNAs may be more abundant and important than previously thought.

Keywords: 5.8S rRNA; RNA sequencing; RT-qPCR; non-coding RNA; small RNA.

MeSH terms

  • 5' Untranslated Regions
  • Animals
  • Cell Line, Tumor
  • Gene Expression Profiling*
  • Gene Expression Regulation
  • Genetic Loci
  • Humans
  • Mice
  • MicroRNAs / genetics*
  • RNA Transport
  • RNA, Ribosomal / genetics*
  • RNA, Ribosomal, 5.8S / genetics
  • RNA, Untranslated / genetics*
  • Ribonucleoproteins / genetics
  • Transcriptome*

Substances

  • 5' Untranslated Regions
  • MicroRNAs
  • RNA, Ribosomal
  • RNA, Ribosomal, 5.8S
  • RNA, Untranslated
  • Ribonucleoproteins