Analysis of the molecular mechanisms involved in the intercellular transfer of double-stranded RNA

2014 Fiscal Year Final Research Report

• Project/Area Number: 24790092
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: The University of Tokyo (2014); Tokyo Women's Medical University (2012-2013)
• Principal Investigator: IMAE Rieko 東京大学, 薬学研究科(研究院), 助教 (60584000)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: RNAi / メンブレントラフィック

Outline of Final Research Achievements

RNA silencing signals in C. elegans spread among cells, leading to RNAi throughout the body. Here, we show that RNAi Spreading Defective-3 (rsd-3), which encodes a homolog of epsinR, a conserved ENTH (epsin N-terminal homology) domain protein, generally participates in cellular uptake of silencing RNA. RSD-3 is previously thought to be involved in systemic RNAi only in germ cells, but we isolated several deletion alleles of rsd-3, and found that these mutants are defective in the spread of silencing RNA not only into germ cells but also into somatic cells. RSD-3 is ubiquitously expressed, and intracellularly localized to the trans-Golgi network (TGN) and endosomes. Tissue-specific rescue experiments indicate that RSD-3 is required for importing silencing RNA into cells rather than exporting from cells. Our results suggest that endomembrane trafficking through the TGN and endosomes generally plays an important role in cellular uptake of silencing RNA.

Free Research Field

分子遺伝学