Intracellular localization and routing of miRNA and RNAi pathway components

Research output: Contribution to journalReview articleContributedpeer-review

Contributors

  • Thomas Ohrt - (Author)
  • Joerg Muetze - , TUD Dresden University of Technology (Author)
  • Petr Svoboda - (Author)
  • Petra Schwille - , TUD Dresden University of Technology (Author)

Abstract

Several different pathways, generally termed RNA silencing pathways, utilize small RNA molecules guiding sequence-specific silencing effects of ribonucleoprotein effector complexes, traditionally termed RNA-induced silencing complex (RISC). Three RNA silencing pathways were recognized in mammalian cells: RNA interference (RNAi), where short RNAs produced from long double-stranded RNA guide cleavage of cognate mRNAs, microRNA (miRNA) pathway, where endogenously-encoded miRNAs typically induce translational repression, and piRNA pathway, where piRNAs (PIWI-associated RNAs) guide repression of repetitive sequences in the germline. Originally, RNAi and miRNA pathways were thought to act in the cytoplasm, however, there is a growing body of evidence that these pathways also have a nuclear component. This text reviews the current evidence concerning nuclear localization and function of miRNA and RNAi pathway components. We provide evidence that TRBP, Dicer and AGO2, proteins found in the RISC-loading complex (RLC) and RISC itself, are present in the nucleus. Nonetheless, fully functional RLC is not found in the nuclear compartment which is consistent with the recent findings obtained by Fluorescence Cross-Correlation Spectroscopy experiments illustrating that RISC is specifically loaded within the cytoplasm and shuttles subsequently between the nuclear and cytoplasmic compartment, thereby allowing small RNA gene regulation in both compartments. The function of nuclear TRBP and Dicer proteins remains elusive. We also discuss the consequences of nucleotide analogs introduced into siRNAs which can severely interfere with the natural cytoplasmic localization mediated by Exportin-5 which is required for efficient RISC loading in the cytoplasm.

Details

Original languageEnglish
Pages (from-to)79-88
Number of pages10
JournalCurrent Topics in Medicinal Chemistry
Volume12
Issue number2
Publication statusPublished - Jan 2012
Peer-reviewedYes
Externally publishedYes

External IDs

PubMed 22196276

Keywords

ASJC Scopus subject areas

Keywords

  • Argonaute 2, Dicer, Fluorescence correlation spectroscopy, Fluorescence crosscorrelation spectroscopy, RISC, RLC, siRNA, TRBP