Conserved tyrosine kinase promotes the import of silencing RNA into Caenorhabditis elegans cells.
RNA silencing in Caenorhabditis elegans is transmitted between cells by the transport of double-stranded RNA (dsRNA). The efficiency of such transmission, however, depends on both the cell type and the environment. Here, we identify systemic RNAi defective-3 (SID-3) as a conserved tyrosine kinase required for the efficient import of dsRNA. Without SID-3, cells perform RNA silencing well but import dsRNA poorly. Upon overexpression of SID-3, cells import dsRNA more efficiently than do wild-type cells and such efficient import of dsRNA requires an intact SID-3 kinase domain. The mammalian homolog of SID-3, activated cdc-42-associated kinase (ACK), acts in many signaling pathways that respond to environmental changes and is known to directly associate with endocytic vesicles, which have been implicated in dsRNA transport. Therefore, our results suggest that the SID-3/ACK tyrosine kinase acts as a regulator of RNA import into animal cells.
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Antony M
AM
Jose
Yunsoo A
YA
Kim
Steven
S
Leal-Ekman
Craig P
CP
Hunter
D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D001692:Biological Transport / Q000502:physiology; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D019295:Computational Biology; D003433:Crosses, Genetic; D017931:DNA Primers / Q000235:genetics; D005838:Genotype; D049452:Green Fluorescent Proteins; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA
D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins; D011505:Protein-Tyrosine Kinases; C576392:SID-3 protein, C elegans