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2017 ; 15
(1
): 54
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Mov10 suppresses retroelements and regulates neuronal development and function in
the developing brain
#MMPMID28662698
Skariah G
; Seimetz J
; Norsworthy M
; Lannom MC
; Kenny PJ
; Elrakhawy M
; Forsthoefel C
; Drnevich J
; Kalsotra A
; Ceman S
BMC Biol
2017[Jun]; 15
(1
): 54
PMID28662698
show ga
BACKGROUND: Moloney leukemia virus 10 (Mov10) is an RNA helicase that mediates
access of the RNA-induced silencing complex to messenger RNAs (mRNAs). Until now,
its role as an RNA helicase and as a regulator of retrotransposons has been
characterized exclusively in cell lines. We investigated the role of Mov10 in the
mouse brain by examining its expression over development and attempting to create
a Mov10 knockout mouse. Loss of both Mov10 copies led to early embryonic
lethality. RESULTS: Mov10 was significantly elevated in postnatal murine brain,
where it bound retroelement RNAs and mRNAs. Mov10 suppressed retroelements in the
nucleus by directly inhibiting complementary DNA synthesis, while cytosolic Mov10
regulated cytoskeletal mRNAs to influence neurite outgrowth. We verified this
important function by observing reduced dendritic arborization in hippocampal
neurons from the Mov10 heterozygote mouse and shortened neurites in the Mov10
knockout Neuro2A cells. Knockdown of Fmrp also resulted in shortened neurites.
Mov10, Fmrp, and Ago2 bound a common set of mRNAs in the brain. Reduced Mov10 in
murine brain resulted in anxiety and increased activity in a novel environment,
supporting its important role in the development of normal brain circuitry.
CONCLUSIONS: Mov10 is essential for normal neuronal development and brain
function. Mov10 preferentially binds RNAs involved in actin binding, neuronal
projection, and cytoskeleton. This is a completely new and critically important
function for Mov10 in neuronal development and establishes a precedent for Mov10
being an important candidate in neurological disorders that have underlying
cytoarchitectural causes like autism and Alzheimer's disease.
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