Regulatory BC1 RNA and the fragile X mental retardation protein: convergent functionality in brain.
BACKGROUND
BC RNAs and the fragile X mental retardation protein (FMRP) are translational repressors that have been implicated in the control of local protein synthesis at the synapse. Work with BC1 and Fmr1 animal models has revealed that phenotypical consequences resulting from the absence of either BC1 RNA or FMRP are remarkably similar. To establish functional interactions between BC1 RNA and FMRP is important for our understanding of how local protein synthesis regulates neuronal excitability.


RESULTS
We generated BC1-/- Fmr1-/- double knockout (dKO) mice. We examined such animals, lacking both BC1 RNA and FMRP, in comparison with single knockout (sKO) animals lacking either one repressor. Analysis of neural phenotypical output revealed that at least three attributes of brain functionality are subject to control by both BC1 RNA and FMRP: neuronal network excitability, epileptogenesis, and place learning. The severity of CA3 pyramidal cell hyperexcitability was significantly higher in BC1-/- Fmr1-/- dKO preparations than in the respective sKO preparations, as was seizure susceptibility of BC1-/- Fmr1-/- dKO animals in response to auditory stimulation. In place learning, BC1-/- Fmr1-/- dKO animals were severely impaired, in contrast to BC1-/- or Fmr1-/- sKO animals which exhibited only mild deficits.


CONCLUSIONS
Our data indicate that BC1 RNA and FMRP operate in sequential-independent fashion. They suggest that the molecular interplay between two translational repressors directly impacts brain functionality.
Department of Physiology and Pharmacology, The Robert F. Furchgott Center for Neural and Behavioral Science, State University of New York Health Science Center at Brooklyn, Brooklyn, New York, USA. jun.zhong@downstate.edu
Jun
J
Zhong
Shih-Chieh
SC
Chuang
Riccardo
R
Bianchi
Wangfa
W
Zhao
Geet
G
Paul
Punam
P
Thakkar
David
D
Liu
André A
AA
Fenton
Robert K S
RK
Wong
Henri
H
Tiedge
D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D001921:Brain / Q000378:metabolism / Q000502:physiology*; D056654:CA3 Region, Hippocampal / Q000378:metabolism / Q000502:physiology; D004594:Electrophysiology / Q000379:methods; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009415:Nerve Net / Q000378:metabolism / Q000502:physiology*; D020733:RNA, Small Cytoplasmic / Q000235:genetics / Q000378:metabolism*
D051860:Fragile X Messenger Ribonucleoprotein 1; D020733:RNA, Small Cytoplasmic; C117734:BC1 RNA