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RNAi pathway is functional in peripheral nerve axons
Author(s) -
Mmashov Alexander K,
Chintalgattu Vishnu,
Islamov Rustem R.,
Lever Teresa E.,
Pak Elena S.,
Sierpinski Paulina L.,
Katwa Laxmansa C.,
Van Scott Michael R.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.06-6155com
Subject(s) - rna interference , translation (biology) , biology , gene silencing , microbiology and biotechnology , rna induced silencing complex , gene knockdown , sciatic nerve , neuroscience , nuclease , rna , messenger rna , anatomy , genetics , gene
Recent observations demonstrated that translation of mRNAs may occur in axonal processes at sites that are long distances away from the neuronal perikaria. While axonal protein synthesis has been documented in several studies, the mechanism of its regulation remains unclear. The aim of this study was to investigate whether RNA interference (RNAi) may be one of the pathways that control local protein synthesis in axons. Here we show that sciatic nerve contains Argonaute2 nuclease, fragile X mental retardation protein, p100 nuclease, and Gemin3 helicase—components of the RNA‐induced silencing complex (RISC). Application of short‐interfering RNAs against neuronal β‐tubulin to the sciatic nerve initiated RISC formation, causing a decrease in levels of neuronal β‐tubulin III mRNA and corresponding protein, as well as a signifi‐cant reduction in retrograde labeling of lumbar motor neurons. Our observations indicate that RNAi is func‐tional in peripheral mammalian axons and is independent from the neuronal cell body or Schwann cells. We introduce a concept of local regulation of axonal translation via RNAi.—Murashov, A. K., Chintalgattu, V., Islamov, R. R., Lever, T. E., Pak, E. S., Sierpinski, P. L., Katwa, L. C., Van Scott, M. R. RNAi pathway is functional in peripheral nerve axons. FASEB J. 21, 656–670 (2007)