期刊
BRAIN RESEARCH
卷 1139, 期 -, 页码 15-28出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2006.12.092
关键词
light neurofilament mRNA; poly(A)-binding protein; aldolase C; multifunctional protein; mRNA stability; neurodegeneration
The multifunctional proteins aldolase C and poly (A)-binding protein (PABP) undergo competitive interactions in cells coexpressing aldolase C and NF-L. A specific in vivo interaction between aldolase C and NF-L mRNA had been localized to a 68 nt segment of the transcript spanning the translation termination signal. It is shown here that the poly (A)binding protein (PABP) binds the body of the NF-L transcript and increases its levels of expression when an excess of PABP is transiently provided in trans. Immunoprecipitation of PABP-associated ribonucleoprotein complexes of human spinal cord pulls down the dimeric form of aldolase C suggesting that their co-regulation of NF-L expression could be linked to the oligomerization status of aldolase C. An ex vivo model of mRNA decay has assessed mechanisms whereby aldolase C and PABP control NF-L expression. This model shows that aldolase C is a zinc-activated ribonuclease that cleaves the transcript at sites closed to the end-terminal structures. Immunological and biochemical depletion of endogenous PABP increases the instability of the transcript suggesting that PABP shields the NF-L mRNA from aldolase attack. An in vitro model shows that a mutant NF-L 68, in which the 45 nt of proximal 31-UTR is replaced with unrelated sequence, is not degraded by aldolase C. Taken together, the findings might have important consequences for understanding causal mechanisms underlying neurodegeneration. (c) 2007 Elsevier B.V. All rights reserved.
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