On BC1 RNA and the fragile X mental retardation protein.
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On BC1 RNA and the fragile X mental retardation protein. / Iacoangeli, Anna; Rozhdestvensky, Timofey S; Dolzhanskaya, Natalia; Tournier, Barthélémy; Schütt, Janin; Brosius, Jürgen; Denman, Robert B; Khandjian, Edouard W; Kindler, Stefan; Tiedge, Henri.
in: P NATL ACAD SCI USA, Jahrgang 105, Nr. 2, 2, 2008, S. 734-739.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - On BC1 RNA and the fragile X mental retardation protein.
AU - Iacoangeli, Anna
AU - Rozhdestvensky, Timofey S
AU - Dolzhanskaya, Natalia
AU - Tournier, Barthélémy
AU - Schütt, Janin
AU - Brosius, Jürgen
AU - Denman, Robert B
AU - Khandjian, Edouard W
AU - Kindler, Stefan
AU - Tiedge, Henri
PY - 2008
Y1 - 2008
N2 - The fragile X mental retardation protein (FMRP), the functional absence of which causes fragile X syndrome, is an RNA-binding protein that has been implicated in the regulation of local protein synthesis at the synapse. The mechanism of FMRP's interaction with its target mRNAs, however, has remained controversial. In one model, it has been proposed that BC1 RNA, a small non-protein-coding RNA that localizes to synaptodendritic domains, operates as a requisite adaptor by specifically binding to both FMRP and, via direct base-pairing, to FMRP target mRNAs. Other models posit that FMRP interacts with its target mRNAs directly, i.e., in a BC1-independent manner. Here five laboratories independently set out to test the BC1-FMRP model. We report that specific BC1-FMRP interactions could be documented neither in vitro nor in vivo. Interactions between BC1 RNA and FMRP target mRNAs were determined to be of a nonspecific nature. Significantly, the association of FMRP with bona fide target mRNAs was independent of the presence of BC1 RNA in vivo. The combined experimental evidence is discordant with a proposed scenario in which BC1 RNA acts as a bridge between FMRP and its target mRNAs and rather supports a model in which BC1 RNA and FMRP are translational repressors that operate independently.
AB - The fragile X mental retardation protein (FMRP), the functional absence of which causes fragile X syndrome, is an RNA-binding protein that has been implicated in the regulation of local protein synthesis at the synapse. The mechanism of FMRP's interaction with its target mRNAs, however, has remained controversial. In one model, it has been proposed that BC1 RNA, a small non-protein-coding RNA that localizes to synaptodendritic domains, operates as a requisite adaptor by specifically binding to both FMRP and, via direct base-pairing, to FMRP target mRNAs. Other models posit that FMRP interacts with its target mRNAs directly, i.e., in a BC1-independent manner. Here five laboratories independently set out to test the BC1-FMRP model. We report that specific BC1-FMRP interactions could be documented neither in vitro nor in vivo. Interactions between BC1 RNA and FMRP target mRNAs were determined to be of a nonspecific nature. Significantly, the association of FMRP with bona fide target mRNAs was independent of the presence of BC1 RNA in vivo. The combined experimental evidence is discordant with a proposed scenario in which BC1 RNA acts as a bridge between FMRP and its target mRNAs and rather supports a model in which BC1 RNA and FMRP are translational repressors that operate independently.
M3 - SCORING: Zeitschriftenaufsatz
VL - 105
SP - 734
EP - 739
JO - P NATL ACAD SCI USA
JF - P NATL ACAD SCI USA
SN - 0027-8424
IS - 2
M1 - 2
ER -
